Table 2.
The inhibition of OATP1B1 and OATP1B2 by antifungal drugs and potential clinical relevance.
| Inhibitor | OATP1B1 IC50 (µM) | 95% CI | OATP1B2 IC50 (µM) | 95% CI | Cmax,ss (µM) a | Citation | Cmax,ss/IC50 (>0.1 Considered Clinically Relevant) |
|---|---|---|---|---|---|---|---|
| Ketoconazole | 1.5 | (1.2, 1.7) | 2.2 | (1.4, 3.4) | 1.88 | [7] | 1.25 |
| Cobicistat | 0.31 | (0.24, 0.40) | 0.7 | (0.57, 0.83) | 1.29 | [27] | 1.84 |
| Ritonavir | 0.34 | (0.29, 0.40) | ND | ND | 1.94 | [28] | 2.71 |
| Rifampin | 1.2 | (0.9, 2.2) | 2.1 | (1.5, 3) | 29 | [29] | 24.2 |
| Itraconazole | 37 | (31, 45) | >50 | ND | 1.15 | [30] | 0.03 |
| Hydroxy-ITZ | 3.5 | (3, 3.9) | >2 | ND | 0.6 | [30] | 0.17 |
| Keto-ITZ | 8.3 | (6.9, 10) | ND | ND | 0.02 | [30] | 0.002 |
| Posaconazole | 1.9 | (1.6, 2.2) | >20 | ND | 2.75 | [31] | 1.45 |
| Voriconazole | 80 | (62, 104) | >200 | ND | 10.2 | [32] | 0.13 |
| Fluconazole | 4100 | (3200, 5300) | >5000 | ND | 61.7 | [33] | 0.06 |
| Isavuconazole | 2.5 | (2.1, 3.0) | 2.5 | (1.1, 5.8) | 8.23 | [34] | 3.29 |
| Micafungin | 2.1 | (1.8, 2.4) | 4.9 | (4.2, 5.7) | 17.3 | [35] | 8.24 |
| Caspofungin | 9.2 | (8.0, 11) | >100 | ND | 7.99 | [36] | 0.87 |
| Anidulafungin | 42 | (31, 57) | ND | ND | 6.14 | [37] | 0.15 |
a Maximum plasma concentration values are representative of clinical regimens used for antifungal prophylaxis. Further information regarding the selection of these values is located in Supplementary Table S2. Abbreviations: Cmax,ss—maximum plasma concentration at steady-state; IC50—half-maximal inhibitory concentration; ND—not determined.