Inhibition of human BSEP and rat Bsep mediated [3H]taurocholate transport by pharmaceuticals
| DILI Class and Drug | Inhibition of hBSEP | Inhibition of rBsep | Cmax, u in Humansa | ||
|---|---|---|---|---|---|
| IC50 | 95% Confidence Limits | IC50 | 95% Confidence Limits | ||
| μM | |||||
| Cholestatic/mixed | |||||
| Acitretin | 18.2 | 8–43 | 19.7 | 11–36 | 0.001 |
| Azathioprine | >1000 | >1000 | 5.049 | ||
| Benoxaprofen | 175.0 | 159–193 | 99.1 | 49–201 | 1.491 |
| Bezafibrate | 231.7 | 140–383 | 391.0 | 187–817 | 0.829 |
| Bosentan | 38.1 | 23–64 | 30.6 | 21–44 | 0.149 |
| Carbamazepine | >1000 | >1000 | 10.158 | ||
| Chlorpromazine | 147.6 | 60–363 | 122.3 | 119–126 | 0.021 |
| Chlorpropamide | >1000 | >1000 | 21.681 | ||
| Ciprofibrate | 572.7 | 325–1009 | 189.9 | 153–236 | 19.194 |
| Clavulanate | >1000 | >1000 | 8.616 | ||
| Cloxacillin | 219.7 | 119–407 | 376.7 | 214–663 | 1.858 |
| Clozapine | 126.1 | 79–200 | 196.5 | 97–396 | 0.122 |
| Cyclosporine | 0.5 | 0.5–0.6 | 0.6 | 0.5–0.6 | 0.054 |
| Dapsone | >1000 | >1000 | 2.175 | ||
| Dicloxacillin | 69.7 | 22–216 | 111.1 | 71–175 | 1.607 |
| d-Penicillamine | >1000 | >1000 | 7.506 | ||
| Erythromycin estolate | 4.1 | 2–11 | 11.4 | 7–18 | 0.210 |
| Famotidine | >1000 | >1000 | 0.492 | ||
| Fenclozic acid | >1000 | >1000 | 9.486 | ||
| Flucloxacillin | 208.6 | 149–293 | 429.1 | 299–616 | 3.305 |
| Flutamide | 143.2 | 27–773 | 78.7 | 28–225 | 0.543 |
| Fusidic acid | 11.5 | 6–21 | 17.4 | 7–42 | 20.127 |
| Glibenclamide | 5.3 | 3–9 | 2.8 | 1–7 | 0.004 |
| Ibuprofen | 598.6 | 218–1645 | 290.9 | 250–338 | 1.454 |
| Iproniazid | >1000 | >1000 | 0.017 | ||
| Ketoconazole | 2.9 | 1–9 | 15.6 | 12–21 | 0.113 |
| Methimazole | >1000 | >1000 | 21.897 | ||
| Nefazodone | 4.2 | 2–11 | 17.4 | 9–32 | 0.043 |
| Nifedipine | 30.7 | 12–76 | 45.4 | 21–100 | 0.012 |
| Nitrofurantoin | >1000 | >1000 | 7.978 | ||
| Nomifensine | >1000 | >1000 | 2.098 | ||
| Pioglitazone | 0.3 | 0.2–0.4 | 2.0 | 1–6 | 0.029 |
| Ranitidine | >1000 | >1000 | 2.703 | ||
| Rifampicin | 11.3 | 5–24 | 34.7 | 9–137 | 2.430 |
| Rifamycin SV | 6.3 | 3–12 | 3.1 | 1–10 | 3.153 |
| Rosiglitazone | 6.4 | 6–7 | 40.0 | 12–129 | 0.002 |
| Sulindac | 226.0 | 173–295 | 87.5 | 37–208 | 2.079 |
| Sulpiride | >1000 | >1000 | 1.054 | ||
| Ticlopidine | 74.0 | 58–94 | 49.0 | 13–192 | 0.283 |
| Tolbutamide | >1000 | >1000 | 14.796 | ||
| Troglitazone | 2.7 | 1–7 | 10.6 | 5–21 | 0.064 |
| Valproate | >1000 | >1000 | 48.540 | ||
| Hepatocellular | |||||
| Acetaminophen | >1000 | >1000 | 165.388 | ||
| Acyclovir | >1000 | >1000 | 18.871 | ||
| Alpidem | 9.2 | 3–33 | 23.0 | 11–50 | 0.006 |
| Carmustine | >1000 | >1000 | 0.008 | ||
| Cinchophen | 695.3 | 296–1634 | 295.8 | 77–1143 | 18.053 |
| Dihydralazine | >1000 | >1000 | 0.645 | ||
| Felbamate | >1000 | >1000 | 0.299 | ||
| Fialuridine | >1000 | >1000 | 0.228 | ||
| Furosemide | >1000 | >1000 | 0.218 | ||
| Glafenine | 22.3 | 10–50 | 32.2 | 29–36 | 0.062 |
| Gliclazide | >1000 | >1000 | 0.711 | ||
| Isoniazid | >1000 | >1000 | 76.564 | ||
| Leflunomide | 177.4 | 134–235 | 111.6 | 68–183 | 1.399 |
| Levofloxacin | >1000 | >1000 | 9.464 | ||
| Methotrexate | >1000 | >1000 | 2.348 | ||
| Methyldopa | >1000 | >1000 | 19.884 | ||
| Probenecid | 564.8 | 231–1382 | 509.9 | 211–1235 | 35.043 |
| Propranolol | >1000 | >1000 | 0.150 | ||
| Salicylic acid | >1000 | >1000 | 362.004 | ||
| Tacrine | >1000 | >1000 | 0.036 | ||
| Tolcapone | 119.6 | 34–418 | 47.2 | 23–98 | 0.476 |
| Zileuton | >1000 | 564.4 | 193–1652 | 0.918 | |
| None | |||||
| Amoxicillin | >1000 | >1000 | 33.661 | ||
| Betaine | >1000 | >1000 | 496.490 | ||
| Buspirone | 104.5 | 55–200 | 369.8 | 184–744 | 0.001 |
| Clobetasol propionate | 8.5 | 5–14 | 35.0 | 14–89 | 0.001 |
| Cromolyn | >1000 | >1000 | 0.192 | ||
| Cycloserine | >1000 | >1000 | 266.432 | ||
| Dexamethasone | 137.4 | 47–399 | 231.9 | 148–363 | 0.072 |
| Donepezil | 205.7 | 93–453 | 519.3 | 256–1055 | 0.002 |
| Dopamine | >1000 | >1000 | 0.077 | ||
| Flumazenil | >1000 | >1000 | 0.561 | ||
| Isoproterenol | >1000 | >1000 | 0.0005 | ||
| Ketotifen | 738.4 | 432–1263 | >1000 | 0.0002 | |
| Methapyrilene | >1000 | >1000 | 0.060 | ||
| Pargyline | >1000 | >1000 | 0.162 | ||
| Physostigmine | >1000 | >1000 | 0.006 | ||
| Picotamide | 441.0 | 238–817 | 636.5 | 200–2026 | 1.288 |
| Pinacidil | 348.1 | 168–721 | 221.6 | 58–851 | 0.183 |
| Practolol | >1000 | >1000 | 13.141 | ||
| Praziquantel | 96.8 | 33–281 | 153.3 | 39–605 | 0.172 |
| Pyridoxine | >1000 | >1000 | 0.122 | ||
| Streptomycin | >1000 | >1000 | 33.529 | ||
↵a Cmax, u values were calculated from the available plasma protein binding and plasma Cmax values. Individual references for these values can be found in Supplemental Table 2.