TABLE 2.
Summary of inhibitory kinetics (IC50) of anti-TB drugs on hOATP1B1- and hOATP2B1-mediated uptake of [3H]ES and hOATP1B3-mediated uptake of [3H]E2Ga
| Anti-TB drug | IC50 (μM) |
||
|---|---|---|---|
| OATP1B1 | OATP2B1 | OATP1B3 | |
| PAS | 72.6 ± 14.0 | ND | 31.5 ± 4.9 |
| Rifabutin | 35.4 ± 2.7 | 57.4 ± 9.4 | 28.8 ± 1.9 |
| Ethambutol | 57.6 ± 3.0 | ND | 53.9 ± 6.7 |
| Linezolid | 65.9 ± 15.9 | 35.6 ± 6.8 | 61.0 ± 7.7 |
| Amoxicillin | 36.2 ± 2.7 | 56.6 ± 5.1 | 28.9 ± 4.5 |
| Clarithromycin | ND | ND | 31.5 ± 4.22 |
| Clofazimine | ND | 56.7 ± 9.6 | 59.0 ± 4.8 |
| Rifampin | 1.9 ± 0.16 | 91.0 ± 14.6 | 6.4 ± 0.5 |
| Amikacin | ND | 55.4 ± 9.5 | ND |
| Kanamycin | ND | 42.9 ± 2.0 | ND |
| Streptomycin | ND | 33.2 ± 2.0 | ND |
| Roxithromycin | ND | 80.0 ± 5.3 | ND |
| Rifapentine | 26.7 ± 4.6 | 36.1 ± 3.5 | 71.0 ± 9.0 |
a
The concentrations of the in vitro prototype substrates [3H]ES and [3H]E2G were 45 and 60 nM, respectively. The corresponding substrate for the transporter was incubated with anti-TB drugs in the concentration range of 1 to 200 μM. Data are presented as means ± SD from three or more independent experiments. The estimated IC50 was calculated by nonlinear kinetics as described in Materials and Methods by using Winnonlin 6.0. ND, not determined.