Covalent binding of tested drugs in HLMs and human hepatocytes in vitro and rat liver in vivo
Data are the mean ± S.D.
Drug No. | Drug | Covalent Binding | ||||
|---|---|---|---|---|---|---|
| HLMs | Human Hepatocytes | Rat Liver in Vivo | ||||
| pmol/mg protein | ||||||
| WDN | ||||||
| 1 | Aminopyrine | 30.9 ± 3.3 | 1.0 ± 0.5 | 555.7 ± 58.1 | ||
| 2 | Amodiaquine | 208.1 ± 13.4 | 91.3 ± 6.1 | 126.3 ± 11.0 | ||
| 3 | Tienilic acida | 439.2 ± 73.2 | N.T. | 46.1 ± 17.5 | ||
| 4 | Zomepirac | 6.4 ± 0.5 | 7.2 ± 0.4 | 28.1 ± 9.1 | ||
| BBW | ||||||
| 5 | Benzbromarone | 389.9 ± 18.9 | 12.1 ± 2.7 | 13.6 ± 1.1 | ||
| 6 | Carbamazepinea | 3.7 ± 0.2 | N.T. | 59.3 ± 4.6 | ||
| 7 | Clozapine | 44.7 ± 2.6 | 82.7 ± 7.7 | 156.6 ± 9.6 | ||
| 8 | Flutamide | 178.0 ± 10.9 | 9.7 ± 0.3 | 59.8 ± 5.0 | ||
| 9 | Nevirapine | 19.1 ± 1.3 | 2.9 ± 1.9 | 79.5 ± 11.4 | ||
| 10 | Ritonavir | 253.3 ± 24.8 | 47.7 ± 3.6 | 68.9 ± 16.3 | ||
| 11 | Ticlopidine | 858.0 ± 25.4 | 89.5 ± 7.8 | 252.0 ± 38.7 | ||
| 12 | Valproic acid | 6.3 ± 3.3 | 9.3 ± 0.7 | 135.7 ± 21.5 | ||
| WNG | ||||||
| 13 | Acetaminophen | 85.2 ± 5.7 | 8.4 ± 1.5 | 10.6 ± 1.6 | ||
| 14 | Atorvastatin | 352.3 ± 60.4 | 209.2 ± 17.1 | 16.9 ± 2.4 | ||
| 15 | Celecoxib | 13.0 ± 2.4 | 7.1 ± 2.5 | 1.4 ± 0.5 | ||
| 16 | Clopidogrel | 417.4 ± 83.1 | 75.0 ± 75.0 | 177.7 ± | ||
| 17 | Diclofenac | 15.9 ± 3.4 | 52.6 ± 2.6 | 23.9 ± 2.7 | ||
| 18 | Erythromycina | 57.1 ± 6.7 | N.T. | 54.5 ± 21.6 | ||
| 19 | Fluoxetine | 15.0 ± 3.9 | 9.0 ± 2.4 | 93.4 ± 10.3 | ||
| 20 | Furosemidea | 78.6 ± 1.4 | N.T. | 14.9 ± 3.3 | ||
| 21 | Imipramine | 133.8 ± 7.0 | 15.5 ± 0.3 | 326.8 ± 86.0 | ||
| 22 | Indomethacina | 16.7 ± 3.2 | N.T. | 26.0 ± 5.6 | ||
| 23 | Phenytoin | 4.4 ± 0.4 | 3.7 ± 2.5 | 34.2 ± 7.6 | ||
| 24 | Procainamidea | 5.1 ± 0.5 | N.T. | 26.5 ± 8.3 | ||
| 25 | Propranolol | 70.0 ± 12.3 | 9.4 ± 0.7 | 87.1 ± 5.3 | ||
| 26 | Sulfamethoxazole | 3.2 ± 0.7 | 0.8 ± 0.1 | 13.2 ± 0.2 | ||
| 27 | Tacrine | 137.0 ± 7.5 | 5.4 ± 0.2 | 46.3 ± 3.3 | ||
| 28 | Tamoxifen | 11.5 ± 2.1 | 64.9 ± 1.5 | 60.8 ± 11.3 | ||
| 29 | Verapamil | 65.6 ± 10.0 | 16.0 ± 0.4 | 42.5 ± 3.8 | ||
| 30 | Zafirlukast | 36.4 ± 2.0 | 19.1 ± 0.9 | 14.2 ± 7.2 | ||
| SAFE | ||||||
| 31 | Amlodipine | 7.3 ± 1.0 | 13.3 ± 1.8 | 1.2 ± 0.5 | ||
| 32 | Caffeine | 9.9 ± 1.6 | 0.2 ± 0.5 | 21.0 ± 3.6 | ||
| 33 | Donepezil | 29.7 ± 0.5 | 13.5 ± 1.1 | 3.9 ± 0.9 | ||
| 34 | Ethinylestradiol | 937.5 ± 94.0 | 80.6 ± 8.3 | 210.2 ± 70.5 | ||
| 35 | Levofloxacin | 0.1 ± 0.5 | 0.0 | 0.0 | ||
| 36 | Olanzapine | 138.9 ± 47.8 | 38.5 ± 0.9 | 93.6 ± 6.4 | ||
| 37 | Olmesartan | 3.4 ± 0.3 | 1.4 ± 0.9 | 0.0 | ||
| 38 | Pioglitazone | 353.0 ± 34.4 | 40.5 ± 14.2 | 6.3 ± 1.7 | ||
| 39 | Pravastatin | 3.7 ± 1.1 | 2.5 ± 0.6 | 9.5 ± 0.6 | ||
| 40 | Rosiglitazone | 516.1 ± 40.3 | 42.5 ± 1.8 | 8.7 ± 0.1 | ||
| 41 | Valsartan | 1.4 ± 0.6 | 0.4 ± 0.2 | 6.3 ± 1.0 | ||
| 42 | Warfarin | 15.9 ± 2.6 | 8.0 ± 1.8 | 17.1 ± 4.5 | ||
N.T., not tested.
↵ a These drugs were not tested in the hepatocyte system because of insufficient purity of the radiolabeled drugs.