Pharmacokinetic parameters of statins and reference compounds
PSact,max refers to the maximal transporter activity in the respective expression system; PSpas refers to the passive permeation; PSact,max/PSpas describes the ratio of the active to passive uptake clearance; and R2 determines the coefficient of determination.
| HEK293-OATP1B1 | HEK293-OATP1B3 | Hepatocytes (lot PQP) | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Compounds | PSact,max | S.D. | PSact,max/PSpas | R2 | PSact,max | S.D. | PSact,max/PSpas | R2 | PSact,max | S.D. | PSact,max/PSpas | R2 |
| (µL/min/mg prot) | (−) | (−) | (µL/min/mg prot) | (−) | (−) | (µL/min/mg prot) | (−) | (−) | ||||
| E3S | 138.1 | 7.2 | 27.7 | 0.99 | 6.7 | 1.9 | 1.2 | 0.93 | 157.7 | 6.1 | 9.6 | 0.99 |
| CCK8 | No substrate | 76.1 | 2.8 | 20.0 | 0.99 | 7.4 | 0.5 | 2.5 | 0.98 | |||
| Atorvastatin | 26.3 | 0.45 | 5.5 | 1.00 | 31.9 | 1.8 | 6.4 | 0.99 | 45.1 | 11.6 | 1.3 | 0.96 |
| Cerivastatin | 8.2 | 1.9 | 0.2 | 0.91 | 8.6 | 1.1 | 0.1 | 0.94 | 54.4 | 3.5 | 0.9 | 0.99 |
| Fluvastatin | 20.9 | 1.8 | 0.5 | 0.96 | 29.8 | 2.0 | 0.5 | 0.98 | 53.7 | 12.1 | 0.7 | 0.88 |
| Lovastatin | 8.9 | 1.0 | 0.4 | 0.92 | No substrate | 40.6 | 4.1 | 1.1 | 0.96 | |||
| Pitavastatin | 33.5 | 3.2 | 1.8 | 0.97 | 14.5 | 3.5 | 0.5 | 0.82 | 89.5 | 11.1 | 1.4 | 0.97 |
| Pravastatin | 10.6 | 3.2 | 6.3 | 0.96 | 2.2 | 0.3 | 1.3 | 0.93 | 13.4 | 1.5 | 7.4 | 0.93 |
| Rosuvastatin | 5.3 | 0.6 | 3.8 | 0.92 | 4.0 | 0.2 | 2.8 | 0.99 | 6.7 | 0.5 | 1.1 | 0.97 |
| Simvastatin | 14.4 | 5.0 | 0.3 | 0.75 | 14.3 | 5.4 | 0.3 | 0.65 | 28.5 | 3.1 | 0.4 | 0.98 |
CCK8, cholecystokinin octapeptide; E3S, estrone-3-sulfate; HEK, human embryonic kidney; OATP, organic anion-transporting polypeptide.