Inhibition of statins to MDR1, Mrp2, MRP2, and OATP1B1 Data are expressed as mean ± SD, n = 3.
Compound | Unbound Cmax | IC50 | ||||||
|---|---|---|---|---|---|---|---|---|
| MDR1 | MRP2 | Mrp2 | OATP1B1 | |||||
| μM | μM | |||||||
| Pravastatin acid | 0.0648a | >100 | >100 | >100 | >100 | |||
| Atorvastatin acid | 0.0024a | >100 | >100 | >100 | 0.87 ± 0.23 | |||
| Atorvastatin lactone | 0.0024b | 14 ± 1 | 15 ± 3 | 15 ± 6 | 2.6 ± 1.4 | |||
| Lovastatin acid | 0.0024a | >100 | >100 | >33 | 4.0 ± 1.2 | |||
| Lovastatin lactone | 0.0025b | 10 ± 4 | >33 | 35 ± 3 | 28 ± 16 | |||
| Simvastatin acid | 0.0039a | >100 | >100 | >100 | 3.6 ± 1.7 | |||
| Simvastatin lactone | 0.0041b | 10 ± 8 | 25 ± 2 | 17 ± 2 | 9.7 ± 0.2 | |||
| Vinblastinc | 29 | 21 | 21 | not applicable | ||||
| Rifamycin SVd |
| not applicable | not applicable | not applicable | 0.23 ± 0.07 | |||
↵ a Based on a 40-mg oral dose. Adapted from data in Corsini et al. (1999)
↵ b The concentration of lactone form was calculated based on the ratio of acid to lactone from other clinical studies (atorvastatin: Mazzu et al., 2000, Kantola et al., 1998a; Iovastatin: Kyrklund et al., 2001; simvastatin: Kantola et al., 1998b)
↵ c Positive control as an inhibitor of MDR1 and MRP/Mrp2 (mean of duplicate experiments)
↵ d Positive control as an inhibitor of OATP1B1