Datasets:
smiles large_stringlengths 1 404 | metric_type large_stringclasses 768
values | reported_value float64 -77 7.4M | reported_units large_stringclasses 556
values | canonical_endpoint_key large_stringclasses 768
values | endpoint_family large_stringclasses 6
values | endpoint_subtype large_stringclasses 10
values | unit_basis large_stringclasses 426
values | target large_stringclasses 161
values | kinetic_parameter large_stringclasses 2
values | defining_timepoint large_stringclasses 13
values | species_exact large_stringclasses 31
values | scalar_value float64 -77 7.4M | unit_normalized large_stringclasses 556
values | scalar_is_approximate bool 2
classes | variation_value float64 0 8.92k ⌀ | variation_type large_stringclasses 1
value | accompanying_interval_lower float64 0.01 2.3k ⌀ | accompanying_interval_upper float64 0.04 3.03k ⌀ | assay_system large_stringlengths 2 114 ⌀ | species large_stringclasses 247
values | molecular_form large_stringlengths 1 61 ⌀ | enzyme_or_pathway large_stringclasses 497
values | qualifying_conditions large_stringlengths 2 166 ⌀ | pmid large_stringlengths 5 8 | confidence large_stringclasses 15
values | source_id large_stringclasses 1
value | source_name large_stringclasses 1
value | record_id large_stringlengths 64 64 | source_row_number int64 5 67.9k | input_sha256 large_stringclasses 1
value | parent_provenance_id large_stringlengths 64 64 | child_id large_stringlengths 64 64 | extra_details large_stringlengths 0 248 | support_text large_stringlengths 39 658 | paragraph_idx large_stringclasses 210
values |
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O=C(Cc1cccc(OC(F)(F)F)c1)Nc1ccc(CCCCc2nnc(NC(=O)Cc3ccccn3)s2)nn1 | q4.hepatic_clearance.intrinsic_clearance.ml_h | 2.61 | ml/h | q4.hepatic_clearance.intrinsic_clearance.ml_h | hepatic_clearance | intrinsic_clearance | ml_h | null | null | null | human | 2.61 | ml/h | true | 0.56 | unspecified_variation | null | null | human liver microsomes | human | null | null | null | 18653746 | 0.96 | q4 | hepatic | fcef11a908dfc9cb5e0a769aeb47e9acdeda8cd608f586127ad9afca59ead5d8 | 5 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | fcef11a908dfc9cb5e0a769aeb47e9acdeda8cd608f586127ad9afca59ead5d8 | ca4c06ae59cf6ce14340bcdf7036126f9df7aabb208ddc8bfd5617938183bf7e | After correcting for the free fraction of GTI-2040 in pooled human liver microsomes, the intrinsic clearance (CLint) calculated as Vmax/Km was estimated to be 2.61 ± 0.56 ml/h. | 37 | |
O=C(Cc1cccc(OC(F)(F)F)c1)Nc1ccc(CCCCc2nnc(NC(=O)Cc3ccccn3)s2)nn1 | q4.hepatic_clearance.intrinsic_clearance.l_h | 182.7 | l/h | q4.hepatic_clearance.intrinsic_clearance.l_h | hepatic_clearance | intrinsic_clearance | l_h | null | null | null | human | 182.7 | l/h | false | null | null | null | null | scaled from human liver microsomes using microsomal protein scaling factor | human | null | null | null | 18653746 | 0.96 | q4 | hepatic | bd5c002c29fb29d046b4f9cc1a26e072f7dca261f41eadbfb4c3b8383ea2cc86 | 7 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | bd5c002c29fb29d046b4f9cc1a26e072f7dca261f41eadbfb4c3b8383ea2cc86 | ff692f1e3c28b113b41a809f7befcc1855b4eaa83138edbf453dbe25be0d1df6 | Predicted value represents 24.1 % of the observed in‑vivo intrinsic clearance. | In this fashion, the predicted in‑vivo CLint,h1 was determined to be 182.7 l/h, which represented 24.1% of the observed CLint,h in patients. | 40 |
CC(C)c1cccc(C(C)C)c1O | q4.hepatic_clearance.intrinsic_clearance.ml_min_body | 1,061 | ml/min/body | q4.hepatic_clearance.intrinsic_clearance.ml_min_body | hepatic_clearance | intrinsic_clearance | ml_min_body | null | null | null | null | 1,061 | ml/min/body | true | 127 | unspecified_variation | null | null | microsomes | null | null | glucuronidation | null | 16763826 | 0.97 | q4 | hepatic | e4cfcedbba500e2cef73225b63ef87e0abe7e7121b45b31ea1ada080664876c3 | 25 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | e4cfcedbba500e2cef73225b63ef87e0abe7e7121b45b31ea1ada080664876c3 | b0b731b50903e682be788652ca257b093c0a3aa9bd1873b5531ff430c84f1533 | Table 2 lists the intrinsic clearance of propofol in liver microsomes for the glucuronidation pathway as Vmax/Km/fumic = 1061 ± 127 ml/min/body. | 28 | |
CC(C)c1cccc(C(C)C)c1O | q4.hepatic_clearance.intrinsic_clearance.ml_min_body | 6,811 | ml/min/body | q4.hepatic_clearance.intrinsic_clearance.ml_min_body | hepatic_clearance | intrinsic_clearance | ml_min_body | null | null | null | null | 6,811 | ml/min/body | true | 729 | unspecified_variation | null | null | microsomes | null | null | hydroxylation | null | 16763826 | 0.96 | q4 | hepatic | 70afdb09c307612b3a24a2ac575374999dba4791b7e3343fd39b84dd78e6b48f | 26 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | 70afdb09c307612b3a24a2ac575374999dba4791b7e3343fd39b84dd78e6b48f | 6a7bd3f284f32242e31f6fe1480fdb46244424b18afe6f3bb73a5038179e6d97 | Table 2 gives the intrinsic clearance of propofol in liver microsomes for the hydroxylation pathway as Vmax/Km/fumic = 6811 ± 729 ml/min/body. | 28 | |
CC(C)c1cccc(C(C)C)c1O | q4.hepatic_clearance.hepatic_clearance.ml_min_body | 6.3 | ml/min/body | q4.hepatic_clearance.hepatic_clearance.ml_min_body | hepatic_clearance | hepatic_clearance | ml_min_body | null | null | null | human | 6.3 | ml/min/body | true | 0.8 | unspecified_variation | null | null | in vivo (human) | human | null | cyp | null | 16763826 | 0.97 | q4 | hepatic | db0984f0b8e8f3f21179dd4e7c8586af0e200e1e762b3d84030b9e59bfccb263 | 29 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | db0984f0b8e8f3f21179dd4e7c8586af0e200e1e762b3d84030b9e59bfccb263 | 22d94a210e14f962a50ed5594d3a8d4471b2c61d89d9d2790bc639823c94a420 | Clearance from liver attributed to oxidation (CYP-mediated) for propofol. | The estimated values of CLh,cyp, CLh,glu, and CLr,glu were 6.3±0.8, 8.8±1.2, and 6.4±2.3 ml/min/body, respectively (Table 3). | 45 |
CC(C)c1cccc(C(C)C)c1O | q4.hepatic_clearance.hepatic_clearance.ml_min_body | 8.8 | ml/min/body | q4.hepatic_clearance.hepatic_clearance.ml_min_body | hepatic_clearance | hepatic_clearance | ml_min_body | null | null | null | human | 8.8 | ml/min/body | true | 1.2 | unspecified_variation | null | null | in vivo (human) | human | null | ugt | null | 16763826 | 0.97 | q4 | hepatic | d09ec935a8bf2515bfe0f101ac540f28cc0a56a61e4066a8078e62e9c81668d4 | 30 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | d09ec935a8bf2515bfe0f101ac540f28cc0a56a61e4066a8078e62e9c81668d4 | 1ceb0bf05432c7ab4b0cc4470a613a7ee0dbd11c70dae89c82b70ca9773fda48 | Clearance from liver attributed to glucuronidation (UGT-mediated) for propofol. | The estimated values of CLh,cyp, CLh,glu, and CLr,glu were 6.3±0.8, 8.8±1.2, and 6.4±2.3 ml/min/body, respectively (Table 3). | 45 |
CC(C)c1cccc(C(C)C)c1O | q4.hepatic_clearance.hepatic_clearance.ml_min_kg | 16.6 | ml/min/kg | q4.hepatic_clearance.hepatic_clearance.ml_min_kg | hepatic_clearance | hepatic_clearance | ml_min_kg | null | null | null | human | 16.6 | ml/min/kg | true | 2.2 | unspecified_variation | null | null | in vivo | human | null | null | null | 16763826 | 0.97 | q4 | hepatic | c45f9873985c4ecc89b440c4b6c4b0f8aa79eef0580efc184c50623d15d077a1 | 31 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | c45f9873985c4ecc89b440c4b6c4b0f8aa79eef0580efc184c50623d15d077a1 | 646c8aa26a2af4f800d639f070eb8946494f5af395324128419423d3a22408f4 | The in‑vivo pharmacokinetic table reports the total hepatic clearance of propofol in humans as 16.6 ± 2.2 ml/min/kg. | 53 | |
CC(C)c1cccc(C(C)C)c1O | q4.hepatic_clearance.hepatic_clearance.ml_min_kg | 16.6 | ml/min/kg | q4.hepatic_clearance.hepatic_clearance.ml_min_kg | hepatic_clearance | hepatic_clearance | ml_min_kg | null | null | null | human | 16.6 | ml/min/kg | true | 2.2 | unspecified_variation | null | null | in vivo (human) | human | null | null | null | 16763826 | 0.96 | q4 | hepatic | d24cdf75195333aff56de3b79c29e23448b1db918268e17cfd33d77bdf782b0c | 32 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | d24cdf75195333aff56de3b79c29e23448b1db918268e17cfd33d77bdf782b0c | ea87e06abd557de583f0fb593089b2a84522cba7a3155b992b94a4b2e6774008 | Total hepatic clearance of propofol measured in humans. | CLh (ml/min/kg) was reported as 16.6±2.2 in humans (Hiraoka et al. [4]). | 53 |
CC(C)c1cccc(C(C)C)c1O | q4.hepatic_clearance.hepatic_clearance.ml_min_body | 6.3 | ml/min/body | q4.hepatic_clearance.hepatic_clearance.ml_min_body | hepatic_clearance | hepatic_clearance | ml_min_body | null | null | null | human | 6.3 | ml/min/body | true | 0.8 | unspecified_variation | null | null | in vivo | human | null | cyp | null | 16763826 | 0.96 | q4 | hepatic | 5c81f732ddccd424610bab92bc93b562e8713fff3bada1948c0740caef7cf64f | 33 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | 5c81f732ddccd424610bab92bc93b562e8713fff3bada1948c0740caef7cf64f | c22978ee51c502b67ad73f8eaf6398e5c86b511240bb4cf575216a1fcb8fca79 | CLh,cyp represents hepatic clearance via cytochrome P450 oxidation. | The table lists CLh,cyp for propofol as 6.3 ± 0.8 ml/min/body, representing clearance from the liver by oxidation (CYP). | 53 |
CC(C)c1cccc(C(C)C)c1O | q4.hepatic_clearance.hepatic_clearance.ml_min_body | 8.8 | ml/min/body | q4.hepatic_clearance.hepatic_clearance.ml_min_body | hepatic_clearance | hepatic_clearance | ml_min_body | null | null | null | human | 8.8 | ml/min/body | true | 1.2 | unspecified_variation | null | null | in vivo | human | null | ugt | null | 16763826 | 0.96 | q4 | hepatic | 44bad0310adde4e60f9d0ae4b44d4876b09c4b39b784226619c31355577db4fd | 34 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | 44bad0310adde4e60f9d0ae4b44d4876b09c4b39b784226619c31355577db4fd | 23cf3ffcb6e266fe7252815a7965fc808f04b89122c87b74b04c27f71c8fb726 | CLh,glu represents hepatic clearance via UDP‑glucuronosyltransferase. | The table reports CLh,glu for propofol as 8.8 ± 1.2 ml/min/body, representing clearance from the liver by glucuronidation (UGT). | 53 |
C=CC(N)=O | q4.hepatic_clearance.intrinsic_clearance.l_h | 3.87 | l/h | q4.hepatic_clearance.intrinsic_clearance.l_h | hepatic_clearance | intrinsic_clearance | l_h | null | null | null | human | 3.87 | l/h | false | null | null | null | null | pbpk model (human) | human | null | null | null | 24216301 | 0.98 | q4 | hepatic | f753b4a3a06929b6c7f61cbdca3e37337ddf99bafa4571fd40e66c5595b6fbf4 | 63 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | f753b4a3a06929b6c7f61cbdca3e37337ddf99bafa4571fd40e66c5595b6fbf4 | d0e364920d312221f487a199d35f21692f57bd0cf9a9a29accd333925c1a389b | The EPA PBPK model for acrylamide, calibrated with human in vivo data, provides Vmax = 27.1 mg/h and Km = 7 mg/L, from which an intrinsic clearance (Clint) of 3.87 L/h was calculated. | 26 | |
CC(C)(c1ccc(O)cc1)c1ccc(O)cc1 | q4.hepatic_clearance.intrinsic_clearance.l_h | 503 | l/h | q4.hepatic_clearance.intrinsic_clearance.l_h | hepatic_clearance | intrinsic_clearance | l_h | null | null | null | human | 503 | l/h | false | null | null | null | null | pbpk model (human) | human | null | null | null | 24216301 | 0.94 | q4 | hepatic | bcbf2a8f4ce940ddebc8cca09a389e204ec48763c12ed45ad1ca45439376ea77 | 66 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | bcbf2a8f4ce940ddebc8cca09a389e204ec48763c12ed45ad1ca45439376ea77 | e57748aa33038ce7d73b1d85f178fff5476ff4c0d634822e4a2593f154da253e | A PBPK model for Bisphenol A, calibrated with human data, yielded an in vivo intrinsic clearance (Clint) of 503 L/h. | 30 | |
ClC(Cl)Cl | q4.hepatic_clearance.intrinsic_clearance.l_h | 844 | l/h | q4.hepatic_clearance.intrinsic_clearance.l_h | hepatic_clearance | intrinsic_clearance | l_h | null | null | null | human | 844 | l/h | false | null | null | null | null | pbpk model (human) | human | null | null | null | 24216301 | 0.93 | q4 | hepatic | 4206567045e186c9146b1cee4d69237b82705a0fee377d4b97352cb496784122 | 67 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | 4206567045e186c9146b1cee4d69237b82705a0fee377d4b97352cb496784122 | 9728805461037c2e5ae5cdb82980d0f82d20d2785d83e17309f26213c3932e96 | In vitro microsomal Vmax (~200 mg/h) and Km (<0.3 µM) suggested Clint far greater than liver blood flow, approximating hepatic clearance to flow. | A PBPK model for chloroform gave an in vivo intrinsic clearance (Clint) of 844 L/h. | 34 |
CCCCC(CC)COC(=O)c1ccccc1C(=O)OCC(CC)CCCC | q4.hepatic_clearance.intrinsic_clearance.ul_min_million_cells | 2.65 | ul/min/million cells | q4.hepatic_clearance.intrinsic_clearance.ul_min_million_cells | hepatic_clearance | intrinsic_clearance | ul_min_million_cells | null | null | null | human | 2.65 | ul/min/million cells | false | null | null | null | null | human hepatocytes | human | null | null | null | 24216301 | 0.98 | q4 | hepatic | 8fd52094fbfc65f3e0554419c5cf86c3ebf898a5af73696f32b42df4b7802690 | 68 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | 8fd52094fbfc65f3e0554419c5cf86c3ebf898a5af73696f32b42df4b7802690 | 7b6f91e9e47f620362239f2fa1a9cf2b6dadb6a9451263093be0bce6ba4fffd9 | The clearance value was used to calculate a first‑pass hepatic extraction factor (FUB = 0.0008) in a Simcyp ADME prediction. | Wetmore et al. (2012) reported an in vitro human hepatocyte intrinsic clearance for DEHP of 2.65 µL/min/million cells. | 41 |
FC(F)(F)C(Cl)Br | q4.hepatic_clearance.intrinsic_clearance.l_h | 19.8 | l/h | q4.hepatic_clearance.intrinsic_clearance.l_h | hepatic_clearance | intrinsic_clearance | l_h | null | null | null | human | 19.8 | l/h | false | null | null | null | null | human liver microsomes | human | null | null | null | 24216301 | 0.97 | q4 | hepatic | 26206bacf1bb49d12e1a830a0f3ae6db15c76dfc835f8cb59087ad00d6fdc983 | 69 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | 26206bacf1bb49d12e1a830a0f3ae6db15c76dfc835f8cb59087ad00d6fdc983 | cbdd7c429ebb232a6577d402701db6110cc6da7a340fd28a27a56a889c0fe043 | Vmax = 170 pM/min/mg protein; Km = 30 µM | Spracklin et al. (1997) measured a Vmax of 170 pM/min/mg microsomal protein and a Km of 30 µM for halothane metabolism in human liver microsomes, from which they calculated an intrinsic clearance (Clint) of 19.8 L/h. | 45 |
CN1CCCC1c1cccnc1 | q4.hepatic_clearance.hepatic_clearance.l_min | 1.09 | l/min | q4.hepatic_clearance.hepatic_clearance.l_min | hepatic_clearance | hepatic_clearance | l_min | null | null | null | human | 1.09 | l/min | false | null | null | null | null | in vivo pbpk model | human | null | null | null | 24216301 | 0.95 | q4 | hepatic | 28d5fa72d8f639506cda9408d3427465556b5d0b63de03d77dcb7819fd6ab453 | 71 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | 28d5fa72d8f639506cda9408d3427465556b5d0b63de03d77dcb7819fd6ab453 | 7151a4bc8da2140bcb213b598f0f607c2f0fce59132cca2dfcd09a87054e62aa | Model calibrated with in vivo human data | Robinson et al. (1992) estimated a hepatic clearance for nicotine of 1.09 L/min using a PBPK model calibrated with in vivo human data. | 50 |
CN1CCCC1c1cccnc1 | q4.hepatic_clearance.intrinsic_clearance.l_h | 239 | l/h | q4.hepatic_clearance.intrinsic_clearance.l_h | hepatic_clearance | intrinsic_clearance | l_h | null | null | null | human | 239 | l/h | false | null | null | null | null | in vivo derived from hepatic clearance | human | null | null | null | 24216301 | 0.94 | q4 | hepatic | 088665b6e114edce4bee9be1d35843edd6d47cf56441155536f0f4dc2f0f25b1 | 72 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | 088665b6e114edce4bee9be1d35843edd6d47cf56441155536f0f4dc2f0f25b1 | ed2686107cb9121e38814f8e97a7a65d988d02ece3ba1187ecf8d10fff65dd04 | Derived from reported hepatic clearance (Clh) of nicotine | From the hepatic clearance reported by Robinson et al. (1992), an in vivo intrinsic clearance (Clint) for nicotine of 239 L/h was calculated. | 51 |
CCOP(=S)(OCC)Oc1ccc([N+](=O)[O-])cc1 | q4.hepatic_clearance.intrinsic_clearance.l_h | 1.65 | l/h | q4.hepatic_clearance.intrinsic_clearance.l_h | hepatic_clearance | intrinsic_clearance | l_h | null | null | null | human | 1.65 | l/h | false | null | null | null | null | primary human hepatocytes | human | null | null | null | 24216301 | 0.97 | q4 | hepatic | 97889383bed359b7ccd46c36a73904334f693b8f1a5c5052c61dff92d59a2507 | 73 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | 97889383bed359b7ccd46c36a73904334f693b8f1a5c5052c61dff92d59a2507 | c9c0e39682252c78c4da606a0301022bd907b685fbdf534ff7c81175f8cae632 | Rotroff et al. (2010) reported metabolism of parathion in primary human hepatocytes and calculated an intrinsic clearance (Clint) of 1.65 L/h. | 53 | |
CCOP(=S)(OCC)Oc1ccc([N+](=O)[O-])cc1 | q4.hepatic_clearance.intrinsic_clearance.l_h | 64.5 | l/h | q4.hepatic_clearance.intrinsic_clearance.l_h | hepatic_clearance | intrinsic_clearance | l_h | null | null | null | human | 64.5 | l/h | false | null | null | null | null | human pbpk model (scaled from vmax/km) | human | null | null | null | 24216301 | 0.95 | q4 | hepatic | 2632bf3987b2d6a3aa47e9cc890024b08d9fe0cf7e3bcfba7c04a610dcb789c9 | 74 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | 2632bf3987b2d6a3aa47e9cc890024b08d9fe0cf7e3bcfba7c04a610dcb789c9 | 685ab8fdc774950e10de1f207dec2a405130abf74f5acf7480be37593e7442d1 | Clint derived from Vmax and Km values in a PBPK model. | Gentry et al. (2002) used a total Vmax of 40 mg/h/kg⁰.⁷⁵ and a Km of 15 mg/L in a human PBPK model for parathion, from which an intrinsic clearance (Clint) of 64.5 L/h was estimated. | 53 |
ClC=C(Cl)Cl | q4.hepatic_clearance.intrinsic_clearance.l_h | 16.1 | l/h | q4.hepatic_clearance.intrinsic_clearance.l_h | hepatic_clearance | intrinsic_clearance | l_h | null | null | null | human | 16.1 | l/h | false | null | null | null | null | human liver microsomes | human | null | null | null | 24216301 | 0.96 | q4 | hepatic | dcbdbb6a2ae343d69a60bb595effe9450d85c911897c5bce294d339d1218878e | 75 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | dcbdbb6a2ae343d69a60bb595effe9450d85c911897c5bce294d339d1218878e | 06d500ffeafba8c922bd135b4fe31086fa8bf81a02d5c768a9c562b2af81e224 | Lipscomb et al. (1998) determined a Vmax of 0.00016 µmoles/min/mg microsomal protein and a Km of 34.5 µM for TCE metabolism in human liver microsomal preparations, yielding an intrinsic clearance (Clint) of 16.1 L/h. | 59 | |
ClC(Cl)Cl | q4.hepatic_clearance.intrinsic_clearance.l_h | 20,695 | l/h | q4.hepatic_clearance.intrinsic_clearance.l_h | hepatic_clearance | intrinsic_clearance | l_h | null | null | null | null | 20,695 | l/h | false | null | null | null | null | in vivo (clint derived from vmax) and in vitro (derived from km) | null | null | null | null | 24216301 | 0.9 | q4 | hepatic | 3671335943e147a0c52f1d4a680d8c7c85edf0d7a4b43dff1711c4857477de02 | 77 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | 3671335943e147a0c52f1d4a680d8c7c85edf0d7a4b43dff1711c4857477de02 | 896eb07f4352f7a8c7221f76d6fa898918be6a02a28315a0c9636e653f000e77 | In vitro‑based Clint reported as ~13,515 L/h; both values refer to flow‑limited metabolism of chloroform. | Using the in vitro observed Km value together with the in vivo estimated Vmax, the resulting intrinsic clearance (Clint) for chloroform is approximately 20,695 L/h, which is close to the in‑vitro‑based Clint of about 13,515 L/h. | 67 |
CC(=O)C[C@@H](c1ccccc1)c1c(O)c2ccccc2oc1=O | q4.hepatic_clearance.intrinsic_clearance.ul_min_pmol_2c9 | 0.02 | ul/min/pmol 2c9 | q4.hepatic_clearance.intrinsic_clearance.ul_min_pmol_2c9 | hepatic_clearance | intrinsic_clearance | ul_min_pmol_2c9 | null | null | null | human | 0.02 | ul/min/pmol 2c9 | true | 0.002 | unspecified_variation | null | null | human liver microsomes | human | null | null | null | 21725985 | 0.98 | q4 | hepatic | 58c630108ba9a23e6bc15e6ba45b22820358f169e8899e2a6d3d6f0626da6dcc | 88 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | 58c630108ba9a23e6bc15e6ba45b22820358f169e8899e2a6d3d6f0626da6dcc | 16650971452b018ab9775b6e23848d21a7bcb5b68c55e3556ee28bc014841bac | Values are means of 3 incubations ± SD. | Table 1 reports the intrinsic clearance (CLint) of S‑warfarin in human liver microsomes (HLM) as 0.02 ± 0.002 µl/min/pmol 2C9 (mean of 3 incubations ± SD). | 59 |
CC(=O)C[C@@H](c1ccccc1)c1c(O)c2ccccc2oc1=O | q4.hepatic_clearance.intrinsic_clearance.ul_min_pmol_2c9 | 0.75 | ul/min/pmol 2c9 | q4.hepatic_clearance.intrinsic_clearance.ul_min_pmol_2c9 | hepatic_clearance | intrinsic_clearance | ul_min_pmol_2c9 | null | null | null | human | 0.75 | ul/min/pmol 2c9 | true | 0.11 | unspecified_variation | null | null | recombinant cyp2c9+b5 supersomes | human | null | null | null | 21725985 | 0.98 | q4 | hepatic | 964743f1cb883f0451b17bec5cddb37998ef2ad5386874a44ce3539d71d7dba5 | 89 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | 964743f1cb883f0451b17bec5cddb37998ef2ad5386874a44ce3539d71d7dba5 | c5bbcd08c48912d29d34edee7f0fb55607fdac85b76b4dc267986044cbb7faef | Values are means of 3 incubations ± SD. | Table 1 reports the intrinsic clearance (CLint) of S‑warfarin in the recombinant CYP2C9+b5 system as 0.75 ± 0.11 µl/min/pmol 2C9 (mean of 3 incubations ± SD). | 59 |
OC1(CN2CCC(COc3noc4cccc(O[C@@H]5CCOC5)c34)CC2)CCOCC1 | q4.hepatic_clearance.intrinsic_clearance.ul_min_mg_protein | 12 | ul/min/mg protein | q4.hepatic_clearance.intrinsic_clearance.ul_min_mg_protein | hepatic_clearance | intrinsic_clearance | ul_min_mg_protein | null | null | null | human | 12 | ul/min/mg protein | false | null | null | null | null | human liver microsomes | human | null | null | null | 29150544 | 0.97 | q4 | hepatic | 4cb6fb9398854c57de34ead6a9c38fbbe523dfcf66bb1f2bb4d61a2fec4b6865 | 101 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | 4cb6fb9398854c57de34ead6a9c38fbbe523dfcf66bb1f2bb4d61a2fec4b6865 | 060cb4b58f0426c8b7969f68ee6825b82af2053796e36224dd48c5572fc0254d | Formation of metabolite M1 from TBPT in liver microsomes. | Table 1 reports that in human liver microsomes TBPT is converted to M1 with an intrinsic clearance (CLint) of 12 µL/min/mg protein. | 47 |
OC1(CN2CCC(COc3noc4cccc(O[C@@H]5CCOC5)c34)CC2)CCOCC1 | q4.hepatic_clearance.intrinsic_clearance.ul_min_mg_protein | 2.5 | ul/min/mg protein | q4.hepatic_clearance.intrinsic_clearance.ul_min_mg_protein | hepatic_clearance | intrinsic_clearance | ul_min_mg_protein | null | null | null | human | 2.5 | ul/min/mg protein | false | null | null | null | null | human liver microsomes | human | null | null | null | 29150544 | 0.96 | q4 | hepatic | c9a91037f2a0b48a4b6ffc932f1269ff7df316de9b512cbb0b1442c05eb2ca05 | 102 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | c9a91037f2a0b48a4b6ffc932f1269ff7df316de9b512cbb0b1442c05eb2ca05 | 0082a776c182318f15a9d2afb9481fdbf44c5ec490a4ae3bed3eb2b35ad95322 | Formation of metabolite M2 from TBPT in liver microsomes. | Table 1 reports that in human liver microsomes TBPT is converted to M2 with an intrinsic clearance (CLint) of 2.5 µL/min/mg protein. | 47 |
OC1(CN2CCC(COc3noc4cccc(O[C@@H]5CCOC5)c34)CC2)CCOCC1 | q4.hepatic_clearance.intrinsic_clearance.ul_min_mg_protein | 32 | ul/min/mg protein | q4.hepatic_clearance.intrinsic_clearance.ul_min_mg_protein | hepatic_clearance | intrinsic_clearance | ul_min_mg_protein | null | null | null | human | 32 | ul/min/mg protein | false | null | null | null | null | human liver microsomes | human | null | null | null | 29150544 | 0.96 | q4 | hepatic | bf5fadc3e4b845efea32037dbe5419cd052f37f78c7d19f058ba7d39d1f7c47f | 103 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | bf5fadc3e4b845efea32037dbe5419cd052f37f78c7d19f058ba7d39d1f7c47f | 720136fd9ae574e542bc0d0fd4e0013d6379b7025d5fe10d2ac65177d28db36b | Total TBPT consumption intrinsic clearance in liver microsomes. | Table 1 shows that the overall consumption of TBPT in human liver microsomes corresponds to an intrinsic clearance (CLint) of 32 µL/min/mg protein. | 47 |
c1cc(O[C@@H]2CCOC2)c2c(OCC3CCNCC3)noc2c1 | q4.hepatic_clearance.intrinsic_clearance.ul_min_mg_protein | 32 | ul/min/mg protein | q4.hepatic_clearance.intrinsic_clearance.ul_min_mg_protein | hepatic_clearance | intrinsic_clearance | ul_min_mg_protein | null | null | null | human | 32 | ul/min/mg protein | false | null | null | null | null | human liver microsomes | human | null | null | null | 29150544 | 0.96 | q4 | hepatic | 3e5e124b08474b100c84c3717c96c24e0e56a730404d87c9537614a8ea37614f | 104 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | 3e5e124b08474b100c84c3717c96c24e0e56a730404d87c9537614a8ea37614f | a32125da97444a3b1e29a95636e31820549a626132c6202baee2d98e18e32101 | Intrinsic clearance for M1 consumption in liver microsomes. | Table 1 lists a CLint of 32 µL/min/mg protein for the consumption of metabolite M1 in human liver microsomes. | 47 |
OC1(CN2CCC(COc3noc4cccc(O[C@@H]5CCOC5)c34)CC2)CCOCC1 | q4.hepatic_clearance.intrinsic_clearance.ul_min_mg | 32 | ul/min/mg | q4.hepatic_clearance.intrinsic_clearance.ul_min_mg | hepatic_clearance | intrinsic_clearance | ul_min_mg | null | null | null | null | 32 | ul/min/mg | false | null | null | null | null | liver microsomes | null | null | null | null | 29150544 | 0.98 | q4 | hepatic | 0284ddd4be8ccf47d924bf69f463a0194a50e86bf4b1896bcebfeb829ce5f058 | 105 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | 0284ddd4be8ccf47d924bf69f463a0194a50e86bf4b1896bcebfeb829ce5f058 | ccf079e0e6cef6e17fdd318da7cf405dd2e504438e06e58ddf2d2b62b0f66261 | In liver microsomes, the estimated intrinsic clearance (CLint) for TBPT was 32 µl/min/mg. | 50 | |
c1cc(O[C@@H]2CCOC2)c2c(OCC3CCNCC3)noc2c1 | q4.hepatic_clearance.intrinsic_clearance.ul_min_mg | 32 | ul/min/mg | q4.hepatic_clearance.intrinsic_clearance.ul_min_mg | hepatic_clearance | intrinsic_clearance | ul_min_mg | null | null | null | null | 32 | ul/min/mg | false | null | null | null | null | liver microsomes | null | null | null | null | 29150544 | 0.98 | q4 | hepatic | a12512f1e55a40f14a4d483f82bb858ef740e221c2f11c71d291c175757f930f | 106 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | a12512f1e55a40f14a4d483f82bb858ef740e221c2f11c71d291c175757f930f | e1a2dfc9464bcbc6fff30ea8931defc8a925dd93b6f9fa335bd7fbe134bff19c | In liver microsomes, the estimated intrinsic clearance (CLint) for M1 was 32 µl/min/mg. | 50 | |
c1cc(O[C@@H]2CCOC2)c2c(OCC3CCN4CC5(CCOCC5)OC4C3)noc2c1 | q4.hepatic_clearance.intrinsic_clearance.ul_min_mg | 102 | ul/min/mg | q4.hepatic_clearance.intrinsic_clearance.ul_min_mg | hepatic_clearance | intrinsic_clearance | ul_min_mg | null | null | null | null | 102 | ul/min/mg | false | null | null | null | null | liver microsomes | null | null | null | null | 29150544 | 0.98 | q4 | hepatic | 8de9e17e5d0e1b567bded3ae60e227280cf6e9bb0d9cbede17b0ae1873f10c18 | 107 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | 8de9e17e5d0e1b567bded3ae60e227280cf6e9bb0d9cbede17b0ae1873f10c18 | 3214b30590a239e1b074fe7a4d75ae0934f709d087973d2440b9939873b7be05 | In liver microsomes, the estimated intrinsic clearance (CLint) for M2 was 102 µl/min/mg. | 50 | |
OC1(CN2CCC(COc3noc4cccc(O[C@@H]5CCOC5)c34)CC2)CCOCC1 | q4.hepatic_clearance.intrinsic_clearance.ul_min_mg | 32 | ul/min/mg | q4.hepatic_clearance.intrinsic_clearance.ul_min_mg | hepatic_clearance | intrinsic_clearance | ul_min_mg | null | null | null | human | 32 | ul/min/mg | false | null | null | null | null | human liver microsomes | human | null | null | null | 29150544 | 0.97 | q4 | hepatic | c11c05ccee7883b0ce2c82f1bcf63b37c363edbdada88d8c1e09d8caa3c3e7dd | 110 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | c11c05ccee7883b0ce2c82f1bcf63b37c363edbdada88d8c1e09d8caa3c3e7dd | 41b7946a573290a5e01d351907916df4b268c9e1712efa0a6f59121c47597e23 | Table shows for TBPT a CLint of 32 µl/min/mg (used to calculate a scaled CLp of 7.9 ml/min/kg). | 69 | |
c1cc(O[C@@H]2CCOC2)c2c(OCC3CCNCC3)noc2c1 | q4.hepatic_clearance.hepatic_clearance.ml_min_kg | 11 | ml/min/kg | q4.hepatic_clearance.hepatic_clearance.ml_min_kg | hepatic_clearance | hepatic_clearance | ml_min_kg | null | null | null | human | 11 | ml/min/kg | false | null | null | null | null | static model scaling | human | null | null | null | 29150544 | 0.97 | q4 | hepatic | 22bbd096b754a85faa79c44a3178029647d48013a2e349d389b7262cdd86ba60 | 111 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | 22bbd096b754a85faa79c44a3178029647d48013a2e349d389b7262cdd86ba60 | 2de1d1c2f1e53cc0defba978665a9ff189bf8b5e732294d390352d7eddd9d7a7 | For metabolite M1, the scaled metabolic clearance (CLm) is 11 ml/min/kg. | 69 | |
c1cc(O[C@@H]2CCOC2)c2c(OCC3CCN4CC5(CCOCC5)OC4C3)noc2c1 | q4.hepatic_clearance.hepatic_clearance.ml_min_kg | 0.4 | ml/min/kg | q4.hepatic_clearance.hepatic_clearance.ml_min_kg | hepatic_clearance | hepatic_clearance | ml_min_kg | null | null | null | human | 0.4 | ml/min/kg | false | null | null | null | null | static model scaling | human | null | null | null | 29150544 | 0.97 | q4 | hepatic | 9d24161b32717b0fafb4dc2a66a2bb261628ac69a95cf7f52eeab136467b7d37 | 112 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | 9d24161b32717b0fafb4dc2a66a2bb261628ac69a95cf7f52eeab136467b7d37 | 00dbf49bdebc883c887a9a4da105e7cf2ce2bce05dc07abcc8cfde78037ca9cf | For metabolite M2, the scaled metabolic clearance (CLm) is 0.40 ml/min/kg. | 69 | |
c1cc(O[C@@H]2CCOC2)c2c(OCC3CCNCC3)noc2c1 | q4.hepatic_clearance.intrinsic_clearance.ul_min_mg | 32 | ul/min/mg | q4.hepatic_clearance.intrinsic_clearance.ul_min_mg | hepatic_clearance | intrinsic_clearance | ul_min_mg | null | null | null | human | 32 | ul/min/mg | false | null | null | null | null | human liver microsomes | human | null | null | null | 29150544 | 0.96 | q4 | hepatic | 005b56c8621e73dbb63e488e567443493788e8ed081a6de10611ef21b5df7e6a | 113 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | 005b56c8621e73dbb63e488e567443493788e8ed081a6de10611ef21b5df7e6a | ffa41d34dfe4954421189dd5027d743eb74594647e51b365c9715bd7457b9a2a | Additional human liver microsomal CLint for metabolite M1 is 32 µl/min/mg. | 73 | |
c1cc(O[C@@H]2CCOC2)c2c(OCC3CCN4CC5(CCOCC5)OC4C3)noc2c1 | q4.hepatic_clearance.intrinsic_clearance.ul_min_mg | 102 | ul/min/mg | q4.hepatic_clearance.intrinsic_clearance.ul_min_mg | hepatic_clearance | intrinsic_clearance | ul_min_mg | null | null | null | human | 102 | ul/min/mg | false | null | null | null | null | human liver microsomes | human | null | null | null | 29150544 | 0.96 | q4 | hepatic | b96b3290588db0528cdaaf070ddf294784b0cea0ea8dc7499e129daabe142dd3 | 114 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | b96b3290588db0528cdaaf070ddf294784b0cea0ea8dc7499e129daabe142dd3 | 5fc4eddc945d4a0851b66d1160861dc475f8a820632f6105f51cacd0d0bd3d26 | Additional human liver microsomal CLint for metabolite M2 is 102 µl/min/mg. | 73 | |
c1cc(O[C@@H]2CCOC2)c2c(OCC3CCN4CC5(CCOCC5)OC4C3)noc2c1 | q4.hepatic_clearance.intrinsic_clearance.ul_min_mg | 102 | ul/min/mg | q4.hepatic_clearance.intrinsic_clearance.ul_min_mg | hepatic_clearance | intrinsic_clearance | ul_min_mg | null | null | null | human | 102 | ul/min/mg | false | null | null | null | null | human hepatocytes | human | null | null | null | 29150544 | 0.96 | q4 | hepatic | bf791d8be74d356ae0bbc918af993c66dc14710fa6fece2eeb3ced2f55bc56ad | 116 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | bf791d8be74d356ae0bbc918af993c66dc14710fa6fece2eeb3ced2f55bc56ad | 11f8b841ec07aa52522c8935edeb3a868b21f425a6933b251daf17b1a3f842a9 | Total intrinsic clearance measured in human hepatocytes. | The high total intrinsic clearance of M2 was reported as 102 µl/min/mg due to its rapid turnover in human hepatocytes. | 81 |
c1cc(O[C@@H]2CCOC2)c2c(OCC3CCN4CC5(CCOCC5)OC4C3)noc2c1 | q4.hepatic_clearance.hepatic_clearance.ml_min_kg | 0.4 | ml/min/kg | q4.hepatic_clearance.hepatic_clearance.ml_min_kg | hepatic_clearance | hepatic_clearance | ml_min_kg | null | null | null | human | 0.4 | ml/min/kg | false | null | null | null | null | well‐stirred model scaling of in vitro data | human | null | null | null | 29150544 | 0.94 | q4 | hepatic | 615955d8349da2430ca6085def24d7f49e78fc5f7f852a793a854622031e7442 | 117 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | 615955d8349da2430ca6085def24d7f49e78fc5f7f852a793a854622031e7442 | 44797e392703e81769ad9e0ede7385e192f1accab9ef4101a0ae1c9e0382d742 | Predicted hepatic clearance for M2 derived from human hepatocyte intrinsic clearance and plasma protein binding. | Scaled clearance using binding parameters and intrinsic clearance in the well‑stirred model predicted a CLm value of 0.4 ml/min/kg for M2. | 81 |
OC1(CN2CCC(COc3noc4cccc(O[C@@H]5CCOC5)c34)CC2)CCOCC1 | q4.hepatic_clearance.hepatic_clearance.ml_min_kg | 7.9 | ml/min/kg | q4.hepatic_clearance.hepatic_clearance.ml_min_kg | hepatic_clearance | hepatic_clearance | ml_min_kg | null | null | null | human | 7.9 | ml/min/kg | false | null | null | null | null | well‐stirred model scaling of in vitro data | human | null | null | null | 29150544 | 0.94 | q4 | hepatic | 2d52ee56a126d2058bae11965bbeb16332198b8671d91552815dfc0f72644d64 | 118 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | 2d52ee56a126d2058bae11965bbeb16332198b8671d91552815dfc0f72644d64 | c93beed2950070c714407e7299e3dee4d6d4a975e1b5a56a59a03d58708385a6 | Predicted hepatic clearance for TBPT derived from human hepatocyte intrinsic clearance and plasma protein binding. | The same scaling approach predicted a CLm value of 7.9 ml/min/kg for TBPT, more than 10‑fold higher than that for M2. | 81 |
c1cc(O[C@@H]2CCOC2)c2c(OCC3CCN4CC5(CCOCC5)OC4C3)noc2c1 | q4.hepatic_clearance.intrinsic_clearance.ul_min_mg | 2.5 | ul/min/mg | q4.hepatic_clearance.intrinsic_clearance.ul_min_mg | hepatic_clearance | intrinsic_clearance | ul_min_mg | null | null | null | human | 2.5 | ul/min/mg | false | null | null | null | null | null | human | null | null | null | 29150544 | 0.88 | q4 | hepatic | 3671d6c26a648031763c23f683aa4f706c9aacd39c89d7297691500e7d493c9f | 119 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | 3671d6c26a648031763c23f683aa4f706c9aacd39c89d7297691500e7d493c9f | 6cc53a3436eded3ee184b8bda0184244754839a0dab6d76447760899e4630bfa | Formation intrinsic clearance determined experimentally (enzyme kinetic measurements). | The formation intrinsic clearance (CLint formation) for M2 was measured as 2.5 µl/min/mg. | 81 |
C=C1CC2(CCN(C)CC2)O[C@@H]1C | q4.hepatic_clearance.intrinsic_clearance.ml_min_g_liver | 29.1 | ml/min/g liver | q4.hepatic_clearance.intrinsic_clearance.ml_min_g_liver | hepatic_clearance | intrinsic_clearance | ml_min_g_liver | null | null | null | rat | 29.1 | ml/min/g liver | false | null | null | null | null | isolated rat hepatocytes | rat | parent ym796 | null | null | 9950288 | 0.97 | q4 | hepatic | d563a7db3281dbd082d6f260d4fc0da98dd2cb082e5311860fceac1f74f2d155 | 144 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | d563a7db3281dbd082d6f260d4fc0da98dd2cb082e5311860fceac1f74f2d155 | c02c03e039d58546b6981d12dd24c354c91961a93f0f79e7216dcfd717596661 | Calculated from Vmax and Km,app under linear (low‑concentration) conditions. | Using the Vmax (542 nmol/min/g liver) and Km,app (18.6 µM) values obtained from rat hepatocytes, the overall intrinsic hepatic clearance under linear conditions was calculated as CL_int,all = Vmax/Km,app = 29.1 ml/min/g liver. | 43 |
C=C1CC2(CCN(C)CC2)O[C@@H]1C | q4.hepatic_clearance.intrinsic_clearance.ml_min_g_liver | 65.3 | ml/min/g liver | q4.hepatic_clearance.intrinsic_clearance.ml_min_g_liver | hepatic_clearance | intrinsic_clearance | ml_min_g_liver | null | null | null | rat | 65.3 | ml/min/g liver | false | null | null | null | null | isolated rat hepatocytes | rat | parent ym796 (unbound) | null | null | 9950288 | 0.96 | q4 | hepatic | a4375809c1ce88bb0cb356ef80d0b58f6ba58dee02da79735b0cb8bd148a82da | 145 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | a4375809c1ce88bb0cb356ef80d0b58f6ba58dee02da79735b0cb8bd148a82da | 4509bb40192ea49b05a78dd5b535d1cade85ef71952cc8babfc324809dd2df0f | Calculated as CL_int divided by the tissue binding fraction (f_T) at 5 µM. | The intrinsic metabolic clearance for the unbound YM796 in hepatocytes (CL_int/f_T) estimated from CL_int and f_T at the low concentration (5 µM) was 65.3 ml/min/g liver. | 43 |
C=C1CC2(CCN(C)CC2)O[C@@H]1C | q4.hepatic_clearance.intrinsic_clearance.ml_min_g_liver | 38.8 | ml/min/g liver | q4.hepatic_clearance.intrinsic_clearance.ml_min_g_liver | hepatic_clearance | intrinsic_clearance | ml_min_g_liver | null | null | null | rat | 38.8 | ml/min/g liver | false | null | null | null | null | rat liver microsomes | rat | parent ym796 | null | null | 9950288 | 0.95 | q4 | hepatic | fb454957b5ce9f52df2deab28c5256e22fc92e1563d4a7484a5ddd83138bf28e | 146 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | fb454957b5ce9f52df2deab28c5256e22fc92e1563d4a7484a5ddd83138bf28e | 73a12d4b85f71b566ff9ff9bf9d309cf0d213f6c736a454d5d29193b80aa5be3 | Microsomal intrinsic clearance measured in vitro. | The intrinsic metabolic clearance measured in rat liver microsomes was reported as 38.8 ml/min/g liver, which is comparable to the hepatocyte value. | 43 |
C=C1CC2(CCN(C)CC2)O[C@@H]1C | q4.hepatic_clearance.intrinsic_clearance.ul_cellular_space_min_mg_protein | 102 | ul cellular space/min/mg protein | q4.hepatic_clearance.intrinsic_clearance.ul_cellular_space_min_mg_protein | hepatic_clearance | intrinsic_clearance | ul_cellular_space_min_mg_protein | null | null | null | rat | 102 | ul cellular space/min/mg protein | false | null | null | null | null | isolated rat hepatocytes | rat | parent ym796 | null | null | 9950288 | 0.96 | q4 | hepatic | 293e1292e9043d831d7c1e1a5243e71ce61e508a323da433632a6fe985a7f52a | 147 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | 293e1292e9043d831d7c1e1a5243e71ce61e508a323da433632a6fe985a7f52a | 82c8fe9c9b8322179e25a81ee90831f5a4a85ef12364c194a896a556706d4b5d | Value corresponds to low YM796 concentration (5 µM). | The CL_int values obtained from Eq. (8) fell markedly from 102 to 1.5 µl cellular space/min/mg protein as the concentration of YM796 increased from 5 µM to 1000 µM. | 45 |
C=C1CC2(CCN(C)CC2)O[C@@H]1C | q4.hepatic_clearance.intrinsic_clearance.ul_cellular_space_min_mg_protein | 1.5 | ul cellular space/min/mg protein | q4.hepatic_clearance.intrinsic_clearance.ul_cellular_space_min_mg_protein | hepatic_clearance | intrinsic_clearance | ul_cellular_space_min_mg_protein | null | null | null | rat | 1.5 | ul cellular space/min/mg protein | false | null | null | null | null | isolated rat hepatocytes | rat | parent ym796 | null | null | 9950288 | 0.96 | q4 | hepatic | d8099f6eb25070f6644b8f78952dfc67c27e5ed417a9c7c602ae6cd0a95739a7 | 148 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | d8099f6eb25070f6644b8f78952dfc67c27e5ed417a9c7c602ae6cd0a95739a7 | 2e40ac744f1853bd1cd4935c5427a2aa9cbccd7d7cee272572bad680510d0af3 | Value corresponds to high YM796 concentration (1000 µM), indicating saturation of hepatic metabolism. | The CL_int values obtained from Eq. (8) fell markedly from 102 to 1.5 µl cellular space/min/mg protein as the concentration of YM796 increased from 5 µM to 1000 µM. | 45 |
CCCN(CCC)CCc1ccc(O)c(OCCc2ccccc2)c1 | q4.hepatic_clearance.intrinsic_clearance.ml_min_1_mg_1_protein | 0.002 | ml min-1 mg-1 protein | q4.hepatic_clearance.intrinsic_clearance.ml_min_1_mg_1_protein | hepatic_clearance | intrinsic_clearance | ml_min_1_mg_1_protein | null | null | null | human | 0.002 | ml min-1 mg-1 protein | false | null | null | null | null | human liver microsomes (pm‐hlm, lacking cyp2d6 activity) | human | ne‐125 | null | pm‐hlm lacks cyp2d6 activity | 15672756 | 0.96 | q4 | hepatic | 024194697ea86131944bd08f87e07cc7273e90eaee61e262892d1246a7f6f4f2 | 153 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | 024194697ea86131944bd08f87e07cc7273e90eaee61e262892d1246a7f6f4f2 | a822f36992d561acdb15571d6fbdbe7a8fd81ed9a327e8f7cfd377647b63f12c | Table p:18 shows that the total predicted intrinsic clearance for metabolite NE‑125 in PM‑HLM is 0.002 ml min⁻¹ mg⁻¹ protein. | 18 | |
CCCN(CCC)CCc1ccc(O)c(OCCc2ccccc2)c1 | q4.hepatic_clearance.intrinsic_clearance.ml_min_1_mg_1_protein | 0.002 | ml min-1 mg-1 protein | q4.hepatic_clearance.intrinsic_clearance.ml_min_1_mg_1_protein | hepatic_clearance | intrinsic_clearance | ml_min_1_mg_1_protein | null | null | null | human | 0.002 | ml min-1 mg-1 protein | false | null | null | null | null | human liver microsomes (pm‐hlm, lacking cyp2d6 activity) | human | ne‐125 | cyp2c9 | pm‐hlm lacks cyp2d6 activity | 15672756 | 0.95 | q4 | hepatic | fedefb503fd79ccc57dbe37670fb3ce493d6fd7a0c1509c5218bf29d265fd289 | 154 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | fedefb503fd79ccc57dbe37670fb3ce493d6fd7a0c1509c5218bf29d265fd289 | 70a6dc9a8ec5fd85ee0b6779d533111a22976ff64d4bea6d253718787b9b7dc7 | Table p:18 lists a predicted intrinsic clearance of 0.002 ml min⁻¹ mg⁻¹ protein for CYP2C9 in the formation of NE‑125 in PM‑HLM. | 18 | |
CCCN(CCC)CCc1ccc(O)c(OCCc2ccccc2)c1 | q4.hepatic_clearance.intrinsic_clearance.ml_min_1_mg_1_protein | 0.001 | ml min-1 mg-1 protein | q4.hepatic_clearance.intrinsic_clearance.ml_min_1_mg_1_protein | hepatic_clearance | intrinsic_clearance | ml_min_1_mg_1_protein | null | null | null | human | 0.001 | ml min-1 mg-1 protein | false | null | null | null | null | human liver microsomes (pm‐hlm, lacking cyp2d6 activity) | human | ne‐125 | cyp2c19 | pm‐hlm lacks cyp2d6 activity | 15672756 | 0.94 | q4 | hepatic | 438d00da1eba7addd17e629b170441c26ec41808df96d985f8465f5808c870a5 | 155 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | 438d00da1eba7addd17e629b170441c26ec41808df96d985f8465f5808c870a5 | 8d9273258e44b57df2a806ca945c0a27cff844b1089892c22667d85504250dc1 | Table p:18 indicates that CYP2C19 contributes a predicted intrinsic clearance of greater than 0.001 ml min⁻¹ mg⁻¹ protein for NE‑125 in PM‑HLM. | 18 | |
CCCN(CCC)CCc1ccc(OC)c(OCCc2ccccc2)c1.Cl | q4.hepatic_clearance.intrinsic_clearance.ml_min_1_mg_1_protein | 0.872 | ml min-1 mg-1 protein | q4.hepatic_clearance.intrinsic_clearance.ml_min_1_mg_1_protein | hepatic_clearance | intrinsic_clearance | ml_min_1_mg_1_protein | null | null | null | human | 0.872 | ml min-1 mg-1 protein | false | null | null | null | null | pooled human liver microsomes (em-hlm) | human | ne-100 | null | null | 15672756 | 0.97 | q4 | hepatic | f734d91fd2be2fb77994c32427d6c4ec114d5d0326a9b349b1a27679a2bcec18 | 159 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | f734d91fd2be2fb77994c32427d6c4ec114d5d0326a9b349b1a27679a2bcec18 | d79e398db63b124c2fb497db1f32e453f83001c9e8eabba26b5b6885767b70cf | The observed intrinsic clearance of the parent compound NE-100 in extensive metabolizer pooled human liver microsomes (EM-HLM) was 0.872 ml min⁻¹ mg⁻¹ protein. | 59 | |
CCCN(CCC)CCc1ccc(OC)c(OCCc2ccccc2)c1.Cl | q4.hepatic_clearance.intrinsic_clearance.ml_min_1_mg_1_protein | 0.089 | ml min-1 mg-1 protein | q4.hepatic_clearance.intrinsic_clearance.ml_min_1_mg_1_protein | hepatic_clearance | intrinsic_clearance | ml_min_1_mg_1_protein | null | null | null | human | 0.089 | ml min-1 mg-1 protein | false | null | null | null | null | human liver microsomes lacking cyp2d6 activity (pm-hlm) | human | ne-100 | null | null | 15672756 | 0.97 | q4 | hepatic | 8656f5329b1070977ddb7c141fa84837a6a7a463c5c2b66f729f8e7b0dafff2b | 160 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | 8656f5329b1070977ddb7c141fa84837a6a7a463c5c2b66f729f8e7b0dafff2b | 8e886013d3e8cf769276a95b32b46422a025bf33a7f412e43b1bf140da253ada | In human liver microsomes lacking CYP2D6 activity (PM-HLM), the observed intrinsic clearance of NE-100 was 0.089 ml min⁻¹ mg⁻¹ protein. | 59 | |
CCCN(CCC)CCc1ccc(OC)c(OCCc2ccccc2)c1.Cl | q4.hepatic_clearance.intrinsic_clearance.ml_min_1_mg_1_protein | 1.008 | ml min-1 mg-1 protein | q4.hepatic_clearance.intrinsic_clearance.ml_min_1_mg_1_protein | hepatic_clearance | intrinsic_clearance | ml_min_1_mg_1_protein | null | null | null | human | 1.008 | ml min-1 mg-1 protein | false | null | null | null | null | human liver microsomes | human | null | null | null | 15672756 | 0.96 | q4 | hepatic | b72dabcd803752964f593c024037ad5db0028472000ab2943a85d39e95bea90d | 161 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | b72dabcd803752964f593c024037ad5db0028472000ab2943a85d39e95bea90d | e3f1fb56af5c896d4e54cdde829bd41a9affb440cb6963c3755076a3e7f46c68 | EM‑HLM (pooled human liver microsomes) representing extensive metabolizers. | The intrinsic clearance (the predicted CLint·HLM‑total) for EM‑HLM (pooled human liver microsomes) and PM‑HLM (human liver microsomes lacking CYP2D6 activity) was 1.008 and 0.148 ml min⁻¹ mg⁻¹ protein, respectively. | 66 |
CCCN(CCC)CCc1ccc(OC)c(OCCc2ccccc2)c1.Cl | q4.hepatic_clearance.intrinsic_clearance.ml_min_1_mg_1_protein | 0.148 | ml min-1 mg-1 protein | q4.hepatic_clearance.intrinsic_clearance.ml_min_1_mg_1_protein | hepatic_clearance | intrinsic_clearance | ml_min_1_mg_1_protein | null | null | null | human | 0.148 | ml min-1 mg-1 protein | false | null | null | null | null | human liver microsomes | human | null | null | null | 15672756 | 0.96 | q4 | hepatic | 03ba75da09d893d0de687269980a67ae317d19a6ea2b81df85fc4d087f4318fe | 162 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | 03ba75da09d893d0de687269980a67ae317d19a6ea2b81df85fc4d087f4318fe | 80cd19fcec48ede5a2f0b97d78410791a8292ec2d418b688d7f1adf79e28dc67 | PM‑HLM (human liver microsomes lacking CYP2D6 activity) representing poor metabolizers. | The intrinsic clearance (the predicted CLint·HLM‑total) for EM‑HLM (pooled human liver microsomes) and PM‑HLM (human liver microsomes lacking CYP2D6 activity) was 1.008 and 0.148 ml min⁻¹ mg⁻¹ protein, respectively. | 66 |
CCCN(CCC)CCc1ccc(OC)c(OCCc2ccccc2)c1.Cl | q4.hepatic_clearance.intrinsic_clearance.ml_min_1_g_1_liver | 65.2 | ml min-1 g-1 liver | q4.hepatic_clearance.intrinsic_clearance.ml_min_1_g_1_liver | hepatic_clearance | intrinsic_clearance | ml_min_1_g_1_liver | null | null | null | human | 65.2 | ml min-1 g-1 liver | false | null | null | null | null | human liver microsomes | human | null | null | null | 15672756 | 0.96 | q4 | hepatic | ec98972b86d7c93e234871e100a08c5020fffdc57bfda8403b6aa4da7951dbd4 | 164 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | ec98972b86d7c93e234871e100a08c5020fffdc57bfda8403b6aa4da7951dbd4 | fd280a240d4ef70c8fd6eaa243e5ddfa4164cafce787f85ad33c3e1ed4b34c42 | Observed CLint free for NE-100 in EM-HLM. | Observed intrinsic clearance (free) of NE-100 in human liver microsomes from extensive metabolizers (EM-HLM) was reported as 65.2 ml·min⁻¹·g⁻¹ liver. | 72 |
CCCN(CCC)CCc1ccc(OC)c(OCCc2ccccc2)c1.Cl | q4.hepatic_clearance.intrinsic_clearance.ml_min_1_g_1_liver | 65.2 | ml min-1 g-1 liver | q4.hepatic_clearance.intrinsic_clearance.ml_min_1_g_1_liver | hepatic_clearance | intrinsic_clearance | ml_min_1_g_1_liver | null | null | null | human | 65.2 | ml min-1 g-1 liver | false | null | null | null | null | human liver microsomes | human | null | null | null | 15672756 | 0.95 | q4 | hepatic | 0bff3b9b11d76a74069bbf9004891213d5007e5ded83d91f445c66d2c16da046 | 165 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | 0bff3b9b11d76a74069bbf9004891213d5007e5ded83d91f445c66d2c16da046 | e87a330e3f998370d53af6ed454a82480f96b7366fd4f5bc36354328f42cc3d3 | Observed intrinsic clearance of NE‑100 disappearance in EM‑HLM. | Observed CLint. free for EM‑HLM was reported as 65.2 ml min⁻¹ g⁻¹ liver. | 73 |
CCCN(CCC)CCc1ccc(OC)c(OCCc2ccccc2)c1.Cl | q4.hepatic_clearance.intrinsic_clearance.ml_min_1_g_1_liver | 67.8 | ml min-1 g-1 liver | q4.hepatic_clearance.intrinsic_clearance.ml_min_1_g_1_liver | hepatic_clearance | intrinsic_clearance | ml_min_1_g_1_liver | null | null | null | human | 67.8 | ml min-1 g-1 liver | false | null | null | null | null | recombinant cyps | human | null | null | null | 15672756 | 0.95 | q4 | hepatic | 3f626eab772797372e3fd75d1a7639463d6e23f041af3af46683682770b31e88 | 166 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | 3f626eab772797372e3fd75d1a7639463d6e23f041af3af46683682770b31e88 | a33be3c37d943ae6571e75f0003181e9060fa7979fba591babc15fd983161831 | Predicted intrinsic clearance of NE‑100 disappearance using recombinant CYPs and RAF approach for extensive metabolizer microsomes. | Predicted CLint. free for EM‑HLM derived from recombinant CYPs was 67.8 ml min⁻¹ g⁻¹ liver. | 73 |
CCCN(CCC)CCc1ccc(OC)c(OCCc2ccccc2)c1.Cl | q4.hepatic_clearance.intrinsic_clearance.ml_min_1_g_1_liver | 11.6 | ml min-1 g-1 liver | q4.hepatic_clearance.intrinsic_clearance.ml_min_1_g_1_liver | hepatic_clearance | intrinsic_clearance | ml_min_1_g_1_liver | null | null | null | human | 11.6 | ml min-1 g-1 liver | false | null | null | null | null | recombinant cyps | human | null | null | null | 15672756 | 0.95 | q4 | hepatic | b239ec8e6fe11aaea9900b9a754d65dd475eda698c0eba2442e3def539fdb50e | 167 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | b239ec8e6fe11aaea9900b9a754d65dd475eda698c0eba2442e3def539fdb50e | c8db243f344e4307ed3148285766e42111a679fdc563ac3f81a043c0e2129a72 | Predicted intrinsic clearance of NE‑100 disappearance using recombinant CYPs and RAF approach for poor metabolizer microsomes. | Predicted CLint. free for PM‑HLM derived from recombinant CYPs was 11.6 ml min⁻¹ g⁻¹ liver. | 73 |
CCCN(CCC)CCc1ccc(OC)c(OCCc2ccccc2)c1.Cl | q4.hepatic_clearance.intrinsic_clearance.ml_min_1_g_1_liver | 67.8 | ml min-1 g-1 liver | q4.hepatic_clearance.intrinsic_clearance.ml_min_1_g_1_liver | hepatic_clearance | intrinsic_clearance | ml_min_1_g_1_liver | null | null | null | human | 67.8 | ml min-1 g-1 liver | false | null | null | null | null | recombinant cyps | human | null | null | null | 15672756 | 0.94 | q4 | hepatic | 28fb0934eba659e7cb74d240f5a33642eb595dcc5293f8529877861b7851c1b4 | 168 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | 28fb0934eba659e7cb74d240f5a33642eb595dcc5293f8529877861b7851c1b4 | 4e0c3144cae15ce23b43ef4388a51291d81c3569fa8ae9f1ab6bf3ba68fd68ca | Predicted CLint free from kinetic parameters on recombinant CYPs for EM-HLM. | Predicted intrinsic clearance (free) of NE-100 using recombinant CYPs for extensive metabolizers (EM-HLM) was 67.8 ml·min⁻¹·g⁻¹ liver. | 73 |
CCCN(CCC)CCc1ccc(OC)c(OCCc2ccccc2)c1.Cl | q4.hepatic_clearance.intrinsic_clearance.ml_min_1_g_1_liver | 11.6 | ml min-1 g-1 liver | q4.hepatic_clearance.intrinsic_clearance.ml_min_1_g_1_liver | hepatic_clearance | intrinsic_clearance | ml_min_1_g_1_liver | null | null | null | human | 11.6 | ml min-1 g-1 liver | false | null | null | null | null | recombinant cyps | human | null | null | null | 15672756 | 0.94 | q4 | hepatic | 85be0df490c61c2d486fa842a2fadcc0e0bb712c1b49b2312bff1c0f7d35682c | 169 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | 85be0df490c61c2d486fa842a2fadcc0e0bb712c1b49b2312bff1c0f7d35682c | a4bcefa9afbfbf901158c5a4e3990c23c380fe5b8c11fbe7728914e9b5d8b23f | Predicted CLint free from kinetic parameters on recombinant CYPs for PM-HLM. | Predicted intrinsic clearance (free) of NE-100 using recombinant CYPs for poor metabolizers (PM-HLM) was 11.6 ml·min⁻¹·g⁻¹ liver. | 73 |
COc1cccc(C2(O)CCCCC2CN(C)C)c1 | q4.cyp_metabolism.enzyme_contribution.percent.cyp2b6 | 30 | % | q4.cyp_metabolism.enzyme_contribution.percent.cyp2b6 | cyp_metabolism | enzyme_contribution | percent | cyp2b6 | null | null | human | 30 | % | false | null | null | null | null | recombinant cyp enzyme assays (supersomestm) | human recombinant | null | cyp2b6 | co-incubation with sr-9186 (2.5 μm) and thiotepa (10 μm) | 25048637 | 0.9 | q4 | hepatic | a0a49e320e84f9d856577384456d037f2ad414219d8ecb8576a364aa0a05e584 | 172 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | a0a49e320e84f9d856577384456d037f2ad414219d8ecb8576a364aa0a05e584 | 5f7c1d132c06e48cf0e38c98a0a62931c72e1830874b845d4debd864197b1455 | Estimated by subtracting the inhibition observed with SR-9186 alone from the combined inhibition with SR-9186 + thioTEPA. | By co-incubating tramadol with the inhibitors, the contribution of CYP2B6 to N-desmethyltramadol formation was estimated at 30 % after correcting for thioTEPA’s effect on CYP3A4. | 65 |
COc1cccc(C2(O)CCCCC2CN(C)C)c1 | q4.cyp_metabolism.enzyme_contribution.percent.cyp2b6 | 30 | % | q4.cyp_metabolism.enzyme_contribution.percent.cyp2b6 | cyp_metabolism | enzyme_contribution | percent | cyp2b6 | null | null | human | 30 | % | false | null | null | null | null | human liver microsomes | human | null | cyp2b6 | null | 25048637 | 0.92 | q4 | hepatic | 4ad37b89d4c2401cf922000c4f2f740396f3d6b24a8b40756a554bf26db9acf8 | 174 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | 4ad37b89d4c2401cf922000c4f2f740396f3d6b24a8b40756a554bf26db9acf8 | d4015fd1a66c2b091aa92369f72b86da5ee5c3485b1168decb54de7212544989 | Contribution to N-desmethyltramadol formation in HLM, may be overestimated due to lower CYP2D6 activity in this microsomal batch. | In addition to CYP2D6 and CYP3A4, a role for CYP2B6 of about 30% in the HLM metabolism of tramadol to N-desmethyltramadol (NDT) could be identified. | 86 |
CNCCCC(C#N)(c1ccc(OC)c(OC)c1)C(C)C | q4.hepatic_clearance.intrinsic_clearance.ml_min_g_liver | 2.21 | ml/min/g liver | q4.hepatic_clearance.intrinsic_clearance.ml_min_g_liver | hepatic_clearance | intrinsic_clearance | ml_min_g_liver | null | null | null | human | 2.21 | ml/min/g liver | false | null | null | null | null | calculated from in vivo data | human | (s)-d-617 | null | null | 9131722 | 0.95 | q4 | hepatic | c46f202be202a18d2b9cab84f89adfaa25d147348983573707ec0ab5f84ad879 | 191 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | c46f202be202a18d2b9cab84f89adfaa25d147348983573707ec0ab5f84ad879 | 5e81ade0f7c3a164fde46c879530ca7eab9554a2c45bc58f5733843dae7301a4 | Calculated by multiplying the in vivo CLint of verapamil (8.72 mL/min/g liver) by the urinary recovery fraction of D-617 (23.3 % of dose) and normalising to the oral absorption fraction (92 %).; molecule_name: D-617 | The formation clearance for D-617 was calculated as (S)-form: 8.72 × 23.3/92 = 2.21 mL/min/g liver. | 53 |
CCOc1ccccc1C(=O)NCCCN1CCOCC1 | q4.hepatic_clearance.intrinsic_clearance.ml_min_g_liver | 0.0345 | ml/min/g liver | q4.hepatic_clearance.intrinsic_clearance.ml_min_g_liver | hepatic_clearance | intrinsic_clearance | ml_min_g_liver | null | null | null | human | 0.0345 | ml/min/g liver | false | null | null | null | null | dispersion model (in vivo) | human | r-form | null | calculated using urinary recovery of d-703 (0.45%) | 9131722 | 0.94 | q4 | hepatic | a3c3cda2940c52a73533f598c23a84c91620557ca2bc70d7dbb00743a54df8a6 | 192 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | a3c3cda2940c52a73533f598c23a84c91620557ca2bc70d7dbb00743a54df8a6 | a163459bfd1c08835a5d0ee8c2493bdcc3ab9a84727ad395567d8932f8e2b06c | For the (R)-form of D-703, the formation clearance was calculated using the urinary recovery of D-703 (0.45%): 7.05 × 0.45 / 92 = 0.0345 mL/min/g liver. | 66 | |
CNC[C@H](O)c1ccc(O)c(O)c1 | q4.hepatic_clearance.intrinsic_clearance.ml_min_g_liver | 2.4 | ml/min/g liver | q4.hepatic_clearance.intrinsic_clearance.ml_min_g_liver | hepatic_clearance | intrinsic_clearance | ml_min_g_liver | null | null | null | human | 2.4 | ml/min/g liver | false | null | null | null | null | human liver microsomes | human | null | null | null | 9131722 | 0.94 | q4 | hepatic | e3abe72e057ce4ce72cf0448acba1bd5b7fdfcfd668d07b2e8c27cd480026d08 | 193 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | e3abe72e057ce4ce72cf0448acba1bd5b7fdfcfd668d07b2e8c27cd480026d08 | 1d4717bff67d7b70911b3b9ea6e65eb306009ea7f175f901d1a11da7dbbdb9f6 | Bargetzi et al. (1989) measured the formation of monoethylglycinexylidide (MEGX), a major metabolite of lidocaine, in vitro using microsomes prepared from human livers, and reported an intrinsic clearance (CLint,in vitro) of 2.4 mL/min/g liver for this metabolic pathway. | 77 | |
CNC[C@H](O)c1ccc(O)c(O)c1 | q4.hepatic_clearance.intrinsic_clearance.ml_min | 6,970 | ml/min | q4.hepatic_clearance.intrinsic_clearance.ml_min | hepatic_clearance | intrinsic_clearance | ml_min | null | null | null | human | 6,970 | ml/min | false | null | null | null | null | in vitro | human | null | null | null | 9131722 | 0.96 | q4 | hepatic | a4868ecd59015723283a1d6062d66678ea2ee9faba539a92089cd00fa02cc491 | 195 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | a4868ecd59015723283a1d6062d66678ea2ee9faba539a92089cd00fa02cc491 | 081c8a30155944d991fa96a998bbc10449613a6cbb148348aad981fd977dd1c9 | For lidocaine, the *in vitro* intrinsic clearance (CLint) was reported as 6970 mL/min. | 89 | |
CNC[C@H](O)c1ccc(O)c(O)c1 | q4.hepatic_clearance.hepatic_clearance.ml_min | 875 | ml/min | q4.hepatic_clearance.hepatic_clearance.ml_min | hepatic_clearance | hepatic_clearance | ml_min | null | null | null | human | 875 | ml/min | false | null | null | null | null | in vivo | human | null | null | null | 9131722 | 0.96 | q4 | hepatic | 3b3437a5a71cdf5f34c7ab0034a812a3505e7c5a5a15a698b98a2a8928af3393 | 196 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | 3b3437a5a71cdf5f34c7ab0034a812a3505e7c5a5a15a698b98a2a8928af3393 | 6265dcf0f654c6c0aa591b9324c07cc0db17836379532f091d1ff8efff43ffa6 | Calculated as CLtot × fm (1094 × 0.8). | The *in vivo* hepatic clearance (CLh) for lidocaine calculated from CLtot (1094 mL/min) and fm (0.8) was 875 mL/min. | 89 |
CNC[C@H](O)c1ccc(O)c(O)c1 | q4.hepatic_clearance.hepatic_clearance.ml_min | 758 | ml/min | q4.hepatic_clearance.hepatic_clearance.ml_min | hepatic_clearance | hepatic_clearance | ml_min | null | null | null | human | 758 | ml/min | false | null | null | null | null | in vitro prediction (well‐stirred model) | human | null | null | null | 9131722 | 0.95 | q4 | hepatic | 8d84d8586a243c0b5b01f1b72916b6cc848ef0192afb81417c99c8224faec718 | 197 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | 8d84d8586a243c0b5b01f1b72916b6cc848ef0192afb81417c99c8224faec718 | 5f6c0b89e7659e84bd6140f1ccf2f401bb174906b41f0dced337b14c49e8f81b | Using the well‑stirred model, the *in vitro* data for lidocaine yielded a predicted hepatic clearance (CLh) of 758 mL/min. | 89 | |
Oc1nc2cc(Cl)ccc2o1 | q4.hepatic_clearance.hepatic_clearance.ml_min | 110 | ml/min | q4.hepatic_clearance.hepatic_clearance.ml_min | hepatic_clearance | hepatic_clearance | ml_min | null | null | null | human | 110 | ml/min | false | null | null | null | null | in vivo | human | null | cyp2e1 | null | 9131722 | 0.94 | q4 | hepatic | b9a6ce592647202aebaede56c746ad50f923c35ad5b15738a122c5d59e434928 | 203 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | b9a6ce592647202aebaede56c746ad50f923c35ad5b15738a122c5d59e434928 | 095dcf8dd4ae070e9ec77abff359d7bbb647fe099a087535184e8ce7825ea4a6 | 6‑hydroxylation reaction. | For the 6‑hydroxylation of chlorzoxazone mediated by CYP2E1, the hepatic clearance values were 110 mL/min in vitro and 110 mL/min in vivo. | 90 |
Cc1nc(NC(=O)N2CCCC2C(N)=O)sc1-c1ccnc(C(C)(C)C(F)(F)F)c1 | q4.hepatic_clearance.hepatic_clearance.ml_min_kg | 9.9 | ml/min/kg | q4.hepatic_clearance.hepatic_clearance.ml_min_kg | hepatic_clearance | hepatic_clearance | ml_min_kg | null | null | null | rat | 9.9 | ml/min/kg | true | 1 | unspecified_variation | null | null | null | rat | null | null | null | 31422548 | 0.95 | q4 | hepatic | 0258149081a53403ff24c5fc117ad466091e22cf1ef0edc4273fd686357ba49a | 231 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | 0258149081a53403ff24c5fc117ad466091e22cf1ef0edc4273fd686357ba49a | c48dab5f98b2d8fdf9291e924be9b03c1394c97a699e2983dfc1d7c8ea6de492 | In vivo value; mean ± standard deviation. | Table 48 reports the in vivo hepatic clearance (CLah) for BYL719 as 9.9 ± 1 mL/min/kg, measured in rats. | 48 |
COc1c(OCCCN2CCOCC2)ccc2c1N=C(NC(=O)c1cnc(N)nc1)N1CCN=C21 | q4.hepatic_clearance.hepatic_clearance.ml_min_kg | 20.9 | ml/min/kg | q4.hepatic_clearance.hepatic_clearance.ml_min_kg | hepatic_clearance | hepatic_clearance | ml_min_kg | null | null | null | rat | 20.9 | ml/min/kg | true | 1 | unspecified_variation | null | null | null | rat | null | null | null | 31422548 | 0.95 | q4 | hepatic | 452bc38c9af469698f3f86912c8ef98812e911a95d5a6ea5a013de2109d1c009 | 232 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | 452bc38c9af469698f3f86912c8ef98812e911a95d5a6ea5a013de2109d1c009 | f75701a9f555c1ae73ad42c08a267f9a97def46f662b40d68fe6591f1b4150a3 | In vivo value; mean ± standard deviation. | Table 48 reports the in vivo hepatic clearance (CLah) for CQC959 as 20.9 ± 1 mL/min/kg, measured in rats. | 48 |
Cc1nc(NC(=O)N2CCCC2C(N)=O)sc1-c1ccnc(C(C)(C)C(F)(F)F)c1 | q4.hepatic_clearance.intrinsic_clearance.ml_min_kg | 4.7 | ml/min/kg | q4.hepatic_clearance.intrinsic_clearance.ml_min_kg | hepatic_clearance | intrinsic_clearance | ml_min_kg | null | null | null | rat | 4.7 | ml/min/kg | true | 0.6 | unspecified_variation | null | null | rat hepatocyte relay (lc‐ms) | rat | null | null | null | 31422548 | 0.94 | q4 | hepatic | d7b124c9f0d11ed4909a1d761daf83795dd0b3b32eb1623b71b345e36770f395 | 234 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | d7b124c9f0d11ed4909a1d761daf83795dd0b3b32eb1623b71b345e36770f395 | 0d8ca4d19871f55f5b74929f90bbc6e91bb35842789c0ca036bf6c0f550b1ead | Measured using the LC‑MS analytical technique; mean ± standard deviation. | Table 48 shows the observed intrinsic clearance (CLint) for BYL719 measured by LC‑MS as 4.7 ± 0.60 mL/min/kg in rat hepatocyte relay experiments. | 48 |
COc1c(OCCCN2CCOCC2)ccc2c1N=C(NC(=O)c1cnc(N)nc1)N1CCN=C21 | q4.hepatic_clearance.intrinsic_clearance.ml_min_kg | 12.7 | ml/min/kg | q4.hepatic_clearance.intrinsic_clearance.ml_min_kg | hepatic_clearance | intrinsic_clearance | ml_min_kg | null | null | null | rat | 12.7 | ml/min/kg | true | 0.27 | unspecified_variation | null | null | rat hepatocyte relay (lc‐ram) | rat | null | null | null | 31422548 | 0.94 | q4 | hepatic | a4e5a92d8dcb458c85b18d6d82877cc26a4e11f7bf3a2a629d598f3572170d9a | 235 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | a4e5a92d8dcb458c85b18d6d82877cc26a4e11f7bf3a2a629d598f3572170d9a | 838889ef493a1c2cfb194394a9ee2e34c3d574f46f04d4ec37968503375ad5dd | Measured using the LC‑RAM analytical technique; mean ± standard deviation. | Table 48 shows the observed intrinsic clearance (CLint) for CQC959 measured by LC‑RAM as 12.7 ± 0.27 mL/min/kg in rat hepatocyte relay experiments. | 48 |
COc1c(OCCCN2CCOCC2)ccc2c1N=C(NC(=O)c1cnc(N)nc1)N1CCN=C21 | q4.hepatic_clearance.intrinsic_clearance.ml_min_kg | 13.2 | ml/min/kg | q4.hepatic_clearance.intrinsic_clearance.ml_min_kg | hepatic_clearance | intrinsic_clearance | ml_min_kg | null | null | null | rat | 13.2 | ml/min/kg | true | 2.3 | unspecified_variation | null | null | rat hepatocyte relay (lc‐ms) | rat | null | null | null | 31422548 | 0.94 | q4 | hepatic | 8835cda770d478dd4f897c81e25698790e37ea3732f08c62e36207b9c504ffa2 | 236 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | 8835cda770d478dd4f897c81e25698790e37ea3732f08c62e36207b9c504ffa2 | 098f518a5f8027d2369647b520c21b77db0ff071bdd070c0563922a1ec46866c | Measured using the LC‑MS analytical technique; mean ± standard deviation. | Table 48 shows the observed intrinsic clearance (CLint) for CQC959 measured by LC‑MS as 13.2 ± 2.3 mL/min/kg in rat hepatocyte relay experiments. | 48 |
CNC[C@H](O)c1ccc(O)c(O)c1 | q4.hepatic_clearance.intrinsic_clearance.ml_min | 6,970 | ml/min | q4.hepatic_clearance.intrinsic_clearance.ml_min | hepatic_clearance | intrinsic_clearance | ml_min | null | null | null | null | 6,970 | ml/min | false | null | null | null | null | in vitro | null | null | cyp3a4 | null | 9597163 | 0.96 | q4 | hepatic | 4e23bd9b14b5ccb7729ca3da8bc99fe9bc45e7bf674d1a560f21689d661661f4 | 256 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | 4e23bd9b14b5ccb7729ca3da8bc99fe9bc45e7bf674d1a560f21689d661661f4 | f8117edbf5e876d785d107bf51691b5ce92c7e58ea65f4dd5d80c836d37b248c | For lidocaine, which is metabolized mainly by CYP3A4, the in vitro intrinsic clearance (CLint) is reported as 6970 ml/min. | 54 | |
CNC[C@H](O)c1ccc(O)c(O)c1 | q4.hepatic_clearance.hepatic_clearance.ml_min | 758 | ml/min | q4.hepatic_clearance.hepatic_clearance.ml_min | hepatic_clearance | hepatic_clearance | ml_min | null | null | null | null | 758 | ml/min | false | null | null | null | null | well‐stirred model calculation | null | null | cyp3a4 | null | 9597163 | 0.95 | q4 | hepatic | 776840c1f6b8fe395af3e1d8e113164de1733e7243fcb9f48ac0eccd15c97373 | 257 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | 776840c1f6b8fe395af3e1d8e113164de1733e7243fcb9f48ac0eccd15c97373 | 944fec175058415eb717b6eaae431c4738ef9ae5cade6b3e9e71e020b6fc5cad | Predicted hepatic clearance from in vitro data using Qh = 1500 ml/min and fB = 0.3. | Using the well‑stirred model, the hepatic clearance (CLh) of lidocaine predicted from the in vitro data is 758 ml/min (Qh = 1500 ml/min, fB = 0.3). | 54 |
Oc1nc2cc(Cl)ccc2o1 | q4.hepatic_clearance.hepatic_clearance.ml_min | 110 | ml/min | q4.hepatic_clearance.hepatic_clearance.ml_min | hepatic_clearance | hepatic_clearance | ml_min | null | null | null | null | 110 | ml/min | false | null | null | null | null | in vivo | null | null | cyp2e1 | null | 9597163 | 0.94 | q4 | hepatic | 640e3879f7f1249c45af6c186f745c148de51c51a400aabf04e7da16df6c63dc | 262 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | 640e3879f7f1249c45af6c186f745c148de51c51a400aabf04e7da16df6c63dc | 6d4d3f487530843dcb2dbd99435d596ba0d4d0314572fe9c2bc1aab3925cf5db | For the 6‑hydroxylation of chlorzoxazone mediated by CYP2E1, both in vitro and in vivo clearances were 110 ml/min. | 54 | |
CNC[C@H](O)c1ccc(O)c(O)c1 | q4.hepatic_clearance.hepatic_clearance.ml_min | 953 | ml/min | q4.hepatic_clearance.hepatic_clearance.ml_min | hepatic_clearance | hepatic_clearance | ml_min | null | null | null | null | 953 | ml/min | false | null | null | null | null | well‐stirred model (in vitro scaling) | null | null | null | null | 9597163 | 0.94 | q4 | hepatic | 7860e20afb98e6a93354e0b5ae12bc7e52214c082b5130d5c8c9ef7b549d2b1a | 263 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | 7860e20afb98e6a93354e0b5ae12bc7e52214c082b5130d5c8c9ef7b549d2b1a | 22a6ebeef33aa1123fd2d576382c2ddb9fb7ba9738c317d713053296c007bf6f | Calculated from the in vitro intrinsic clearance (f_B CL_int,all) of 2614 ml/min. | Using the well‑stirred model, hepatic clearance (CL_h) for lidocaine was calculated as 953 ml/min. | 55 |
CNC[C@H](O)c1ccc(O)c(O)c1 | q4.hepatic_clearance.hepatic_clearance.ml_min | 1,100 | ml/min | q4.hepatic_clearance.hepatic_clearance.ml_min | hepatic_clearance | hepatic_clearance | ml_min | null | null | null | null | 1,100 | ml/min | false | null | null | null | null | in vivo | null | null | null | null | 9597163 | 0.94 | q4 | hepatic | 223e5910191c77a824b34767bab581573abc29905402831395bdddd661cf38d3 | 264 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | 223e5910191c77a824b34767bab581573abc29905402831395bdddd661cf38d3 | 0f9739ee85ad2886511b57b9b15dc7b6218f9916faeda0b9f344b9bc529b0ead | Derived by subtracting renal clearance from total clearance. | The observed in vivo hepatic clearance (CL_h) for lidocaine, after subtracting non‑hepatic clearance, was 1100 ml/min. | 55 |
CN(CCCC(=O)c1cccnc1)N=O | q4.cyp_metabolism.enzyme_contribution.percent.cyp1a2 | 46 | % | q4.cyp_metabolism.enzyme_contribution.percent.cyp1a2 | cyp_metabolism | enzyme_contribution | percent | cyp1a2 | null | null | human | 46 | % | false | null | null | null | null | human liver microsomes and cdna‐expressed microsomes (raf method) | human | null | cyp1a2 | null | 9597163 | 0.95 | q4 | hepatic | 47f1525e6a77d9fe6fb66fb3ab6246db0dda4a7101dbc69b28d50d6ef31ba20b | 271 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | 47f1525e6a77d9fe6fb66fb3ab6246db0dda4a7101dbc69b28d50d6ef31ba20b | 5249065ce01fea9cdc9b43add86a9b5bc547ee0d8cf38e6795a67e1eba715f1c | Contribution calculated from intrinsic clearance using the initial slope of the mutagenicity dose‑response curve and RAF values. | Using the RAF approach, the contribution of CYP1A2 to the metabolism of 4-(methylnitrosoamino)-1-(3-pyridyl)-1-butanone (NNK) in human liver was estimated to be 46% of the total intrinsic clearance. | 75 |
CN(CCCC(=O)c1cccnc1)N=O | q4.cyp_metabolism.enzyme_contribution.percent.cyp2a6 | 12 | % | q4.cyp_metabolism.enzyme_contribution.percent.cyp2a6 | cyp_metabolism | enzyme_contribution | percent | cyp2a6 | null | null | human | 12 | % | false | null | null | null | null | human liver microsomes and cdna‐expressed microsomes (raf method) | human | null | cyp2a6 | null | 9597163 | 0.95 | q4 | hepatic | 762932ed60169dbced749e33df9326cc75de147e813fbbf4b4cce81fd0bd37cb | 272 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | 762932ed60169dbced749e33df9326cc75de147e813fbbf4b4cce81fd0bd37cb | 4afb83edb7fd05f4a0bc34945f7dcb960895ffdc602055d4079d55d8fe251817 | Contribution calculated from intrinsic clearance using the initial slope of the mutagenicity dose‑response curve and RAF values. | Using the RAF approach, the contribution of CYP2A6 to the metabolism of 4-(methylnitrosoamino)-1-(3-pyridyl)-1-butanone (NNK) in human liver was estimated to be 12% of the total intrinsic clearance. | 75 |
CN(CCCC(=O)c1cccnc1)N=O | q4.cyp_metabolism.enzyme_contribution.percent.cyp2d6 | 1 | % | q4.cyp_metabolism.enzyme_contribution.percent.cyp2d6 | cyp_metabolism | enzyme_contribution | percent | cyp2d6 | null | null | human | 1 | % | false | null | null | null | null | human liver microsomes and cdna‐expressed microsomes (raf method) | human | null | cyp2d6 | null | 9597163 | 0.95 | q4 | hepatic | d90557ca11ca3c0e798f310080d618fd4951f6d03a9d93bf933794048a8bb6d3 | 273 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | d90557ca11ca3c0e798f310080d618fd4951f6d03a9d93bf933794048a8bb6d3 | a77a9c218387706e1fe3ab83a1d2aa54fa8b5a9de8023f05252e25cd5bba5c9c | Contribution calculated from intrinsic clearance using the initial slope of the mutagenicity dose‑response curve and RAF values. | Using the RAF approach, the contribution of CYP2D6 to the metabolism of 4-(methylnitrosoamino)-1-(3-pyridyl)-1-butanone (NNK) in human liver was estimated to be 1% of the total intrinsic clearance. | 75 |
CN(CCCC(=O)c1cccnc1)N=O | q4.cyp_metabolism.enzyme_contribution.percent.cyp2e1 | 41 | % | q4.cyp_metabolism.enzyme_contribution.percent.cyp2e1 | cyp_metabolism | enzyme_contribution | percent | cyp2e1 | null | null | human | 41 | % | false | null | null | null | null | human liver microsomes and cdna‐expressed microsomes (raf method) | human | null | cyp2e1 | null | 9597163 | 0.95 | q4 | hepatic | 82036f6c42c286b8cf7651ebf998c2aad413b77f63f93f670b2ea698960deaca | 274 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | 82036f6c42c286b8cf7651ebf998c2aad413b77f63f93f670b2ea698960deaca | 5dd21008433ad30fb4a25fa7e82c06b3f50b38922643c2c36a621e73696471b6 | Contribution calculated from intrinsic clearance using the initial slope of the mutagenicity dose‑response curve and RAF values. | Using the RAF approach, the contribution of CYP2E1 to the metabolism of 4-(methylnitrosoamino)-1-(3-pyridyl)-1-butanone (NNK) in human liver was estimated to be 41% of the total intrinsic clearance. | 75 |
Cc1[nH]cnc1CN1CCc2c(c3cccc(F)c3n2C)C1=O.Cl | q4.hepatic_clearance.intrinsic_clearance.ml_min_kg | 75 | ml/min/kg | q4.hepatic_clearance.intrinsic_clearance.ml_min_kg | hepatic_clearance | intrinsic_clearance | ml_min_kg | null | null | null | rat | 75 | ml/min/kg | true | 15 | unspecified_variation | null | null | microsomes | rat | null | null | null | 17701833 | 0.99 | q4 | hepatic | ebdaae937a15df019e031e8f272507b00d800507a6b4f2c7ebbce4af18a08476 | 317 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | ebdaae937a15df019e031e8f272507b00d800507a6b4f2c7ebbce4af18a08476 | 46ba13cba32bf0fc927ec9469731e8020939b2b5f05e1eac2a1f0e4dc96247d0 | In rat microsomes, GR87442 showed an intrinsic clearance of 75 ± 15 ml/min/kg. | 38 | |
Cc1[nH]cnc1CN1CCc2c(c3cccc(F)c3n2C)C1=O.Cl | q4.hepatic_clearance.intrinsic_clearance.ml_min_kg | 21 | ml/min/kg | q4.hepatic_clearance.intrinsic_clearance.ml_min_kg | hepatic_clearance | intrinsic_clearance | ml_min_kg | null | null | null | dog | 21 | ml/min/kg | true | 13 | unspecified_variation | null | null | microsomes | dog | null | null | null | 17701833 | 0.99 | q4 | hepatic | 3b5b09ae6e380335843869ddb1250aea417dc900ba0ee70210f3694705be3d00 | 318 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | 3b5b09ae6e380335843869ddb1250aea417dc900ba0ee70210f3694705be3d00 | 1ee7348d34ae1351b1abb5925f662d717844206220ccbe87f19ff0ebf151ce7c | In dog microsomes, GR87442 showed an intrinsic clearance of 21 ± 13 ml/min/kg. | 38 | |
Cc1[nH]cnc1CN1CCc2c(c3cccc(F)c3n2C)C1=O.Cl | q4.hepatic_clearance.intrinsic_clearance.ml_min_kg | 148 | ml/min/kg | q4.hepatic_clearance.intrinsic_clearance.ml_min_kg | hepatic_clearance | intrinsic_clearance | ml_min_kg | null | null | null | rat | 148 | ml/min/kg | true | 58 | unspecified_variation | null | null | hepatocytes | rat | null | null | null | 17701833 | 0.99 | q4 | hepatic | 8ffbbf6fe5ac934efc6b4a6571274cab1b05664a2f8323396964f4a74385b51f | 319 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | 8ffbbf6fe5ac934efc6b4a6571274cab1b05664a2f8323396964f4a74385b51f | 09d423933ab5fbefa6c8315addc3c8f9f320d60940aa14f5b72721c9e942460a | In rat hepatocytes, GR87442 showed an intrinsic clearance of 148 ± 58 ml/min/kg. | 38 | |
Cc1[nH]cnc1CN1CCc2c(c3cccc(F)c3n2C)C1=O.Cl | q4.hepatic_clearance.intrinsic_clearance.ml_min_kg | 64 | ml/min/kg | q4.hepatic_clearance.intrinsic_clearance.ml_min_kg | hepatic_clearance | intrinsic_clearance | ml_min_kg | null | null | null | dog | 64 | ml/min/kg | true | 20 | unspecified_variation | null | null | hepatocytes | dog | null | null | null | 17701833 | 0.99 | q4 | hepatic | b7498eb8dfe0dc6880cbf2e0caae75d8883af1ec7f90c45ede783c69b2776119 | 320 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | b7498eb8dfe0dc6880cbf2e0caae75d8883af1ec7f90c45ede783c69b2776119 | 914a843140f6bf9b3394ff33004d296a31120ab1995062ab8a9905eea4d9457b | In dog hepatocytes, GR87442 showed an intrinsic clearance of 64 ± 20 ml/min/kg. | 38 | |
Cc1[nH]cnc1CN1CCc2c(c3cccc(F)c3n2C)C1=O.Cl | q4.hepatic_clearance.hepatic_clearance.ml_min_kg | 40 | ml/min/kg | q4.hepatic_clearance.hepatic_clearance.ml_min_kg | hepatic_clearance | hepatic_clearance | ml_min_kg | null | null | null | rat | 40 | ml/min/kg | true | 23 | unspecified_variation | null | null | hepatocytes | rat | null | null | non‐restrictive model (without fu) | 17701833 | 0.98 | q4 | hepatic | a49dffd1d2fff91b7951102c7e49925218cad2d9ab80fac696029eb5ec607da6 | 321 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | a49dffd1d2fff91b7951102c7e49925218cad2d9ab80fac696029eb5ec607da6 | b76a5be0f96fd6faa9e535ce8207da2bf098e75d9259fe004338283a8407995e | Predicted value compared with in vivo plasma clearance of 15 ml/min/kg. | Using the non‑restrictive model, GR87442 hepatic clearance predicted from rat hepatocytes was 40 ± 23 ml/min/kg. | 43 |
Cc1[nH]cnc1CN1CCc2c(c3cccc(F)c3n2C)C1=O.Cl | q4.hepatic_clearance.hepatic_clearance.ml_min_kg | 25 | ml/min/kg | q4.hepatic_clearance.hepatic_clearance.ml_min_kg | hepatic_clearance | hepatic_clearance | ml_min_kg | null | null | null | dog | 25 | ml/min/kg | true | 3.1 | unspecified_variation | null | null | hepatocytes | dog | null | null | non‐restrictive model (without fu) | 17701833 | 0.98 | q4 | hepatic | 1eaab4060513c9594ef6485cfec8a33b1b84fa1dfa6cb2c3243c3c430077cbdd | 322 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | 1eaab4060513c9594ef6485cfec8a33b1b84fa1dfa6cb2c3243c3c430077cbdd | 1df34a522d84916d95ea89a7639031e9872ee7a4d8702dc58cbe40ba73bd37a0 | Predicted value compared with in vivo plasma clearance of 8 ml/min/kg. | Using the non‑restrictive model, GR87442 hepatic clearance predicted from dog hepatocytes was 25 ± 3.1 ml/min/kg. | 43 |
Cc1[nH]cnc1CN1CCc2c(c3cccc(F)c3n2C)C1=O.Cl | q4.hepatic_clearance.hepatic_clearance.ml_min_kg | 6.9 | ml/min/kg | q4.hepatic_clearance.hepatic_clearance.ml_min_kg | hepatic_clearance | hepatic_clearance | ml_min_kg | null | null | null | rat | 6.9 | ml/min/kg | true | 1.2 | unspecified_variation | null | null | microsomes | rat | null | null | restrictive model (including fu) | 17701833 | 0.97 | q4 | hepatic | 1d810120ef066a130b2b7bb365a1ad6fcb1a76a2f395f7bbe65fce226fd452f7 | 324 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | 1d810120ef066a130b2b7bb365a1ad6fcb1a76a2f395f7bbe65fce226fd452f7 | ba1ac1ef1f7669c5d0a79a56816f675a13bb4816e1cf76e08b5e9cfb2ba01c32 | Compared with in vivo plasma clearance of 15 ml/min/kg. | Using the restrictive model, GR87442 hepatic clearance predicted from rat microsomes was 6.9 ± 1.2 ml/min/kg. | 46 |
CN1C(=O)CN=C(c2ccc(O)cc2)c2cc(Cl)ccc21 | q4.hepatic_clearance.intrinsic_clearance.ul_min_mg_protein | 39.9 | ul/min/mg protein | q4.hepatic_clearance.intrinsic_clearance.ul_min_mg_protein | hepatic_clearance | intrinsic_clearance | ul_min_mg_protein | null | null | null | rat | 39.9 | ul/min/mg protein | true | 27.6 | unspecified_variation | null | null | rat liver microsomes | rat | 4'hdz | null | null | 8553684 | 0.96 | q4 | hepatic | fa3948f1ea0ca1d1214e0587c42a1d7209afdb5e6636bbb2a1671cfa4e1051bb | 340 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | fa3948f1ea0ca1d1214e0587c42a1d7209afdb5e6636bbb2a1671cfa4e1051bb | 4cdd24eaed383ce67e135fe43152ecfb9e69eb6ad5d11ce373c3fd5341f2fe8a | Mean ± SD, n = 4. | In rat hepatic microsomes the intrinsic clearance (CLint) for the 4'HDZ metabolite was 39.9 ± 27.6 µL/min per mg of microsomal protein. | 39 |
O=C1CN=C(c2ccccc2)c2cc(Cl)ccc2N1 | q4.hepatic_clearance.intrinsic_clearance.ul_min_mg_protein | 22.3 | ul/min/mg protein | q4.hepatic_clearance.intrinsic_clearance.ul_min_mg_protein | hepatic_clearance | intrinsic_clearance | ul_min_mg_protein | null | null | null | rat | 22.3 | ul/min/mg protein | true | 1.9 | unspecified_variation | null | null | rat liver microsomes | rat | ndz | null | null | 8553684 | 0.96 | q4 | hepatic | fa18d5aba1f4fbaaf4edce2288e8dfd26ecc102f842399149e8ed2b4e727d1b7 | 342 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | fa18d5aba1f4fbaaf4edce2288e8dfd26ecc102f842399149e8ed2b4e727d1b7 | 4f400cc22a3fe97282db3f48480b2e2aa1f7563dcee99ce7801460b8eff91311 | Mean ± SD, n = 4. | In rat hepatic microsomes the intrinsic clearance (CLint) for the NDZ metabolite was 22.3 ± 1.9 µL/min per mg of microsomal protein. | 39 |
CN1C(=O)CN=C(c2ccc(O)cc2)c2cc(Cl)ccc21 | q4.hepatic_clearance.intrinsic_clearance.ul_min_10_6_cells | 57.9 | ul/min/10^6 cells | q4.hepatic_clearance.intrinsic_clearance.ul_min_10_6_cells | hepatic_clearance | intrinsic_clearance | ul_min_10_6_cells | null | null | null | rat | 57.9 | ul/min/10^6 cells | true | 9.1 | unspecified_variation | null | null | rat hepatocytes | rat | 4'hdz | null | null | 8553684 | 0.96 | q4 | hepatic | 43e9127b625e421b52450e39c022192746c58eba85a1cb3723fada9943a1bc9f | 343 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | 43e9127b625e421b52450e39c022192746c58eba85a1cb3723fada9943a1bc9f | 0c5fe3132382f206495f58436a50feae1267ef80d25c3eed526e960364060b70 | Mean ± SD, n = 4. | In rat hepatic hepatocytes the intrinsic clearance (CLint) for the 4'HDZ metabolite was 57.9 ± 9.1 µL/min per million cells. | 39 |
COc1cc2c(c3oc(=O)c4c(c13)CCC4=O)[C@@H]1C=CO[C@@H]1O2 | q4.hepatic_clearance.hepatic_clearance.l_h | 40 | l/h | q4.hepatic_clearance.hepatic_clearance.l_h | hepatic_clearance | hepatic_clearance | l_h | null | null | null | human | 40 | l/h | false | null | null | null | null | human liver microsomes | human | cyp3a4-mediated | cyp3a4 | null | 36110298 | 0.96 | q4 | hepatic | 4c9726b07f4f266bccd3e39d1178f764bee7eba5b9436c1bab199016567027d8 | 353 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | 4c9726b07f4f266bccd3e39d1178f764bee7eba5b9436c1bab199016567027d8 | 24585263a2189dc7735e4e9a47767601d94433475a51279469b2e5abde2be752 | The hepatic blood clearance (CLH,B) for aflatoxin B1 mediated by CYP3A4 in human liver microsomes (HLM) was 40.0 L/h. | 0 | |
COc1cc2c(c3oc(=O)c4c(c13)CCC4=O)[C@@H]1C=CO[C@@H]1O2 | q4.hepatic_clearance.hepatic_clearance.l_h | 38.5 | l/h | q4.hepatic_clearance.hepatic_clearance.l_h | hepatic_clearance | hepatic_clearance | l_h | null | null | null | human | 38.5 | l/h | false | null | null | null | null | human liver microsomes | human | cyp1a2-mediated | cyp1a2 | null | 36110298 | 0.96 | q4 | hepatic | 51fb1270e789c481a21039be53cb08850858eed15f31aaa075c268196fab6a9b | 354 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | 51fb1270e789c481a21039be53cb08850858eed15f31aaa075c268196fab6a9b | 364a6ab413f63a788fd3a48d8b193957afa28d005ca932b30eb26c406fc3143b | The hepatic blood clearance (CLH,B) for aflatoxin B1 mediated by CYP1A2 in human liver microsomes (HLM) was 38.5 L/h. | 0 | |
COc1cc2c(c3oc(=O)c4c(c13)CCC4=O)[C@@H]1C=CO[C@@H]1O2 | q4.cyp_metabolism.enzyme_contribution.percent.cyp3a4_3a5 | 45 | % | q4.cyp_metabolism.enzyme_contribution.percent.cyp3a4_3a5 | cyp_metabolism | enzyme_contribution | percent | cyp3a4_3a5 | null | null | human | 45 | % | false | null | null | null | null | human liver microsomes | human | null | cyp3a4/3a5 | null | 36110298 | 0.95 | q4 | hepatic | 74ee3870457fcd3c1e7d597336eebaf8733830620e313ba2926962957a52c5c1 | 355 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | 74ee3870457fcd3c1e7d597336eebaf8733830620e313ba2926962957a52c5c1 | 5383743c8d2d78cf51db14739b48ce0d0cd88b8884f76961bfc66c702b47b9ff | Inhibition assay in HLM | Inhibition assays in human liver microsomes showed that 45% of aflatoxin B1 metabolism was performed by CYP3A4/3A5 enzymes. | 0 |
COc1cc2c(c3oc(=O)c4c(c13)CCC4=O)[C@@H]1C=CO[C@@H]1O2 | q4.cyp_metabolism.enzyme_contribution.percent.cyp1a2 | 49 | % | q4.cyp_metabolism.enzyme_contribution.percent.cyp1a2 | cyp_metabolism | enzyme_contribution | percent | cyp1a2 | null | null | human | 49 | % | false | null | null | null | null | human liver microsomes | human | null | cyp1a2 | null | 36110298 | 0.95 | q4 | hepatic | eb011754bdca8f5d70da8926c6c43563ce0fb872bab986ff6873a9e2bc81f2ba | 356 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | eb011754bdca8f5d70da8926c6c43563ce0fb872bab986ff6873a9e2bc81f2ba | 1071e41660ed05695c9c8e86253090b967977ad8892ab19393aead6752a11919 | Inhibition assay in HLM | Inhibition assays in human liver microsomes showed that 49% of aflatoxin B1 metabolism was performed by CYP1A2 enzymes. | 0 |
COc1cc2c(c3oc(=O)c4c(c13)CCC4=O)[C@@H]1C=CO[C@@H]1O2 | q4.hepatic_clearance.intrinsic_clearance.ul_min_mg | 282 | ul/(min*mg) | q4.hepatic_clearance.intrinsic_clearance.ul_min_mg | hepatic_clearance | intrinsic_clearance | ul_min_mg | null | null | null | human | 282 | ul/(min*mg) | false | null | null | null | null | human liver microsomes | human | null | null | null | 36110298 | 0.96 | q4 | hepatic | c758fa29db5dd9dc9a8fc5c9e0f58b355aa6fc6a8e23d7b475b7a47e967a185a | 357 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | c758fa29db5dd9dc9a8fc5c9e0f58b355aa6fc6a8e23d7b475b7a47e967a185a | bb9386278a3548fbc6f297c38f56cdf6d98ed1b9aa3f8f09ba2d28c5de2a6011 | The in‑vitro intrinsic clearance (CLint,in vitro) measured in human liver microsomes (HLM) for aflatoxin B1 (AFB1) was reported as 282 μl/(min·mg). | 57 | |
COc1cc2c(c3oc(=O)c4c(c13)CCC4=O)[C@@H]1C=CO[C@@H]1O2 | q4.hepatic_clearance.hepatic_clearance.l_h | 1,190 | l/h | q4.hepatic_clearance.hepatic_clearance.l_h | hepatic_clearance | hepatic_clearance | l_h | null | null | null | human | 1,190 | l/h | false | null | null | null | null | human liver microsomes | human | null | null | null | 36110298 | 0.95 | q4 | hepatic | e3074192b9a23879ca967847301cafaf3da9d23e761d54ca4fb6c4a57ecd61df | 360 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | e3074192b9a23879ca967847301cafaf3da9d23e761d54ca4fb6c4a57ecd61df | 5e178546fbdb7b989f82b420ae807e83e254485816275b178e39fce2b3878cd6 | Intrinsic (unbound) hepatic clearance obtained by scaling the in‑vitro CLint. | The unbound intrinsic hepatic clearance (CLH,u,int) derived from HLM data for aflatoxin B1 (AFB1) was calculated as 1,190 L/h. | 57 |
COc1cc2c(c3oc(=O)c4c(c13)CCC4=O)[C@@H]1C=CO[C@@H]1O2 | q4.hepatic_clearance.hepatic_clearance.l_h | 40 | l/h | q4.hepatic_clearance.hepatic_clearance.l_h | hepatic_clearance | hepatic_clearance | l_h | null | null | null | human | 40 | l/h | false | null | null | null | null | human liver microsomes | human | null | cyp3a4 | null | 36110298 | 0.94 | q4 | hepatic | a9c6bc4b192617e69fe19823b5b17488579b8111d2cfca21467b4a4101c70627 | 363 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | a9c6bc4b192617e69fe19823b5b17488579b8111d2cfca21467b4a4101c70627 | 2b6ef0485751fd2745795b4d2ea6e3e3e5f3e6ce1c911cddc7e1c957dbf92f6c | For aflatoxin B1 (AFB1) examined in HLM and attributed to CYP3A4, the hepatic blood clearance (CLH,B) was calculated as 40.0 L/h. | 61 | |
COc1cc2c(c3oc(=O)c4c(c13)CCC4=O)[C@@H]1C=CO[C@@H]1O2 | q4.hepatic_clearance.hepatic_clearance.l_h | 38.5 | l/h | q4.hepatic_clearance.hepatic_clearance.l_h | hepatic_clearance | hepatic_clearance | l_h | null | null | null | human | 38.5 | l/h | false | null | null | null | null | human liver microsomes | human | null | cyp1a2 | null | 36110298 | 0.94 | q4 | hepatic | 336b2be20b3a5769c1b61671204a99c0ca925a26e9295e0ce8ea2a1644bd433f | 364 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | 336b2be20b3a5769c1b61671204a99c0ca925a26e9295e0ce8ea2a1644bd433f | 1640381d12ad26add1b29e6b430b27571362209255150efa23399787cae0ad61 | For aflatoxin B1 (AFB1) examined in HLM and attributed to CYP1A2, the hepatic blood clearance (CLH,B) was calculated as 38.5 L/h. | 61 | |
COc1cc2c(c3oc(=O)c4c(c13)CCC4=O)[C@@H]1C=CO[C@@H]1O2 | q4.hepatic_clearance.hepatic_clearance.l_h | 47.7 | l/h | q4.hepatic_clearance.hepatic_clearance.l_h | hepatic_clearance | hepatic_clearance | l_h | null | null | null | human | 47.7 | l/h | false | null | null | null | null | recombinant cyp3a4 supersomes | human (recombinant) | null | cyp3a4 | null | 36110298 | 0.93 | q4 | hepatic | 43c0c2290a6bb97e3381e9a6c379188fee1f746d80dfdf49ec281475315abd91 | 366 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | 43c0c2290a6bb97e3381e9a6c379188fee1f746d80dfdf49ec281475315abd91 | 45fc3f6d297219019f6edf7d1dab0b9f660b149bdb2aed2c5f8aed81d0ad0875 | Using recombinant CYP3A4 supersomes, the hepatic blood clearance (CLH,B) for aflatoxin B1 (AFB1) was calculated as 47.7 L/h. | 61 | |
COc1cc2c(c3oc(=O)c4c(c13)CCC4=O)[C@@H]1C=CO[C@@H]1O2 | q4.hepatic_clearance.hepatic_clearance.l_h | 56.1 | l/h | q4.hepatic_clearance.hepatic_clearance.l_h | hepatic_clearance | hepatic_clearance | l_h | null | null | null | human | 56.1 | l/h | false | null | null | null | null | recombinant cyp1a2 bactosomes | human (recombinant) | null | cyp1a2 | null | 36110298 | 0.93 | q4 | hepatic | 1f51ac685cf9184e567649968fb0d161549c0397ab651c22c7216f5214be8add | 367 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | 1f51ac685cf9184e567649968fb0d161549c0397ab651c22c7216f5214be8add | 8e41cd6f2fde9fe5d6b114b95fbdb99360f22876ac409d24e8df3b69f79b402f | Using EasyCYP bactosomes expressing CYP1A2, the hepatic blood clearance (CLH,B) for aflatoxin B1 (AFB1) was calculated as 56.1 L/h. | 61 |
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Hepatic Cleaned
This dataset contains 17,637 accepted finite scalar measurement children from the versioned canonical-base pipeline. A parent row with several unambiguous measurements can produce several child rows. Rejected, malformed, ambiguous, bounded, range-only, TDC-overlapping, and endpoint-unassignable records are not published here.
Cleaning
The following source columns are replaced in place with validated canonical or lexical normalizations:
smiles→canonical_smilesmetric_type→canonical_endpoint_keyassay_system→assay_system_normalizedspecies→species_normalizedmolecular_form→molecular_form_normalizedreported_units→unit_normalizedenzyme_or_pathway→enzyme_or_pathway_normalizedqualifying_conditions→qualifying_conditions_normalizedreported_value→scalar_value
The public column names on the left are retained; the names on the right identify the validated internal values used to replace them. Columns omitted from this dataset:
extraction_id:internal_identifierglobal_identifier:internal_identifierdirection:all_null_in_datasetauc_window:all_null_in_dataset
canonical_endpoint_key is the endpoint identity field. No condition_key is added.
species_exact is populated only for explicit, unambiguous species references. Narrative
and other source fields without a validated normalization remain source text.
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