Effect of plasma on the uptake clearance in wild-type and OATP1B1-transfected HEK293 cells
Statistical significance of plasma-induced increase in uptake clearance was assessed using unpaired t test (*P < 0.05; **P < 0.01; ***P < 0.001).
| Uptake PSinf,u in HEK–Wild-Type Cells (µl/min per milligram) | Uptake PSinf,u in HEK-OATP1B1 Cells (µl/min per milligram) | Uptake Ratio (OATP1B1/WT) | |||||||
|---|---|---|---|---|---|---|---|---|---|
| Buffer, Mean (%CV)a | Plasma, Mean (%CV)a | Plasma/Buffer Ratiob | Buffer, Mean (%CV)a | Plasma, Mean (%CV)a | Plasma/Buffer Ratiob | Buffer | Plasma | Plasma/Buffer Ratio | |
| Atorvastatin | 12.2 (26) | 29.1 (14)** | 2.4 | 111.4 (31) | 228.0 (11)** | 2.0 | 9.1 | 7.8 | 0.9 |
| Bosentan | 17.8 (24) | 14.7 (10) | 0.8 | 29.5 (34) | 27.3 (6) | 0.9 | 1.7 | 1.9 | 1.1 |
| Cerivastatin | 31.7 (7) | 60.7 (14)** | 1.9 | 54.7 (14) | 104.2 (9)** | 1.9 | 1.7 | 1.7 | 1.0 |
| Entacapone | 22.0 (32) | 147.3 (18)** | 6.7 | 54.2 (6) | 403.6 (12)*** | 7.5 | 2.5 | 2.7 | 1.1 |
| Fluvastatin | 26.8 (23) | 23.0 (27) | 0.9 | 52.6 (36) | 82.4 (23) | 1.6 | 2.0 | 3.6 | 1.8 |
| Pitavastatin | 8.3 (5) | 27.6 (12)*** | 3.3 | 60.1 (18) | 139.7 (16)** | 2.3 | 7.3 | 5.1 | 0.7 |
| Pravastatin | 0.2 (76) | 0.2 (42) | 1.2 | 1.7 (32) | 1.8 (41) | 1.1 | 9.5 | 8.9 | 0.9 |
| Repaglinide | 17.1 (24) | 65.0 (15)** | 3.8 | 25.7 (28) | 58.1 (18)** | 2.3 | 1.5 | 0.9 | 0.6 |
| Rosuvastatin | 0.1 (56) | 0.2 (33) | 1.4 | 4.1 (35) | 4.7 (45) | 1.2 | 46.8 | 31.0 | 0.7 |
| Telmisartan | 84.0 (19) | 106.6 (32) | 1.3 | 97.1 (9) | 202.6 (14)** | 2.1 | 1.2 | 1.9 | 1.6 |
| Midazolam | 26.3 (16) | 13.1 (75) | 0.5 | 32.0 (15) | 10.1 (2) | 0.3 | 1.2 | 0.8 | 0.6 |
| Tolbutamide | 1.2 (25) | 6.76 (32)* | 5.5 | 1.1 (40) | 5.1 (17)** | 4.8 | 0.9 | 0.8 | 0.9 |
a Mean and S.D. from three independent experiments, with each run in triplicate.
b Ratio ≥ 2.0 was arbitrarily assumed to be of meaningful increase in uptake PSinf,u.