The Ki values for OATP1B1-mediated pitavastatin uptake and the prediction of the possibility of DDI by considering the maximum plasma unbound concentration at the inlet to the liver
The Ki values are expressed as mean ± computer-calculated S.D. R value = 1 + fu· Iin,max/Ki.
Inhibitor | Ki Value for OATP1B1 | R Value |
|---|---|---|
| μM | ||
| Cyclosporin A | 0.242 ± 0.029 | 3.55 |
| Tacrolimus | 0.611 ± 0.069 | 1.20 |
| Rifampicin | 0.477 ± 0.030 | 13.4 |
| Rifamycin SV | 0.171 ± 0.024 | 65.6 |
| Tolbutamide | >100 | <1.21 |
| Glibenclamide | 0.746 ± 0.101 | 1.00 |
| Fluconazole | >100 | <1.25 |
| Ketoconazole | 19.2 ± 3.9 | 1.03 |
| Itraconazole | >100 | <1.00 |
| Gemfibrozil | 25.2 ± 4.7 | 1.08 |
| Gemfibrozil-1-O-glucuronide | 22.6 ± 5.8 | 1.10a |
| Gemfibrozil-M3 | >300 | <1.03a |
| Clofibrate | >300 | <1.03 |
| Ciprofibrate | 141 ± 22 | 1.01 |
| Bezafibrate | 68.6 ± 11.9 | 1.03 |
| Fenofibrate | >300 | <1.00 |
| Cimetidine | >300 | <1.14 |
| Ranitidine | >300 | <1.16 |
| Valsartan | 8.96 ± 1.33 | 1.10 |
| Telmisartan | 0.436 ± 0.043 | 1.16 |
| Chlorzoxazone | >100 | <1.00 |
| Colchichine | >100 | <1.07 |
| Phenytoin | >100 | <1.03 |
| Clarithromycin | 8.26 ± 0.54 | 3.29 |
| Erythromycin | 11.4 ± 2.1 | 1.25 |
| Indinavir | 18.4 ± 1.9 | 2.77 |
| Ritonavir | 0.781 ± 0.048 | 2.25 |
| Saquinavir | 1.59 ± 0.13 | 1.62 |
| Probenecid | 76.2 ± 7.1 | 1.85 |
| Methotrexate | >300 | <1.01 |
| Digoxin | 31.7 ± 3.0 | 1.00 |
| Diltiazem | >100 | <1.03 |
| Verapamil | 51.6 ± 15.9 | 1.02 |
| Warfarin | 83.3 ± 9.7 | 1.00 |
↵ a These values were calculated by using the reported values for the maximum plasma concentration of inhibitors in the clinical situations, instead of Iin,max, because we did not have enough parameters to estimate the Iin,max value.