Drug | Vmaxa | Kma | Vmax/Km | PSdifa | Kp,uu,V0b | fT,cell,V0b |
---|---|---|---|---|---|---|
pmol/min/106 Cells | μM | μL/min/106 Cells | μL/min/106 Cells | |||
Pitavastatin | 893 ± 124 | 5.43 ± 1.29 | 164 ± 45 | 3.00 ± 1.41 | 55.8 ± 29.9 | 0.172 ± 0.131 |
Rosuvastatin | 250 ± 80 | 2.86 ± 1.82 | 87.4 ± 62.3 | 1.76 ± 1.15 | 50.7 ± 48.0 | 0.649 ± 0.688 |
Pravastatin | 178 ± 11 | 20.3 ± 1.4 | 8.77 ± 0.81 | 1.16 ± 0.08 | 8.56 ± 0.87 | 0.685 ± 0.428 |
↵a The initial uptake rate in rat hepatocytes was calculated from the uptake of [3H]pitavastatin, [3H]rosuvastatin, and [3H]pravastatin for 0.5–1.5 minutes. Kinetic parameters are obtained by fitting to the data at seven concentrations (0.1, 0.3, 1, 3, 10, 30, and 100 µM for all statins; Supplemental Fig. 2) using eq. 4.
↵b The Kp,uu,V0 and fT,cell,V0 were calculated using eqs. 5 and 6, respectively. C/M ratios at 37°C (Table 2) were used for the calculation of the fT,cell,V0.