Comparison of in vitro uptake clearance in plated human hepatocytes across three different hepatocyte lots for a representative six OATP1B1 substrates
Statistical significance of plasma-induced increase in uptake clearance was assessed using unpaired t test (*P < 0.05; **P < 0.01; ***P < 0.001).
| Compound | Lot HH1062 | Lot HH1025 | Lot Hu8246a | ||||||
|---|---|---|---|---|---|---|---|---|---|
| Uptake PSinf,u in PHH | Plasma/Buffer Ratio (R value) | Uptake PSinf,u in PHH | Plasma/Buffer Ratio (R Value) | Uptake PSinf,u in PHH | Plasma/Buffer Ratio (R Value) | ||||
| Buffer (µl/min per milligram, %CV)b | Plasma (µl/min per milligram, %CV)b | Buffer (µl/min per milligram, %CV)b | Plasma (µl/min per milligram, %CV)b | Buffer (µl/min per milligram, %CV) | Plasma (µl/min per milligram, %CV) | ||||
| Fluvastatin | 26.2 (12) | 56.9 (27)* | 2.2 | 31.4 (19) | 55.4 (16)* | 1.8 | 51.9 (40) | 116 (37) | 2.2 |
| Glyburide | 20.6 (9) | 46.8 (11)*** | 2.3 | 53.6 (8) | 90.7 (10)** | 1.7 | 42.0 (9) | 105 (37)* | 2.5 |
| Montelukast | 117.1 (20) | 2318 (15)*** | 19.8 | 246.3 (35) | 4244 (5)*** | 17.2 | 129 (18) | 2010 (17)*** | 15.6 |
| Pitavastatin | 45.2 (38) | 160.8 (20)** | 3.6 | 47.7 (34) | 157.9 (19)** | 3.3 | 36.3 (21) | 129 (10)*** | 3.6 |
| PF-05241328 | 20.3 (12) | 109.8 (21)** | 5.4 | 24.4 (13) | 78 (31)* | 3.2 | 52.0 (14) | 320 (36)* | 6.2 |
| Rosuvastatin | 8.9 (19) | 8.5 (12) | 1.0 | 7.6 (14) | 7.50 (9) | 1.0 | 7.8 (15) | 7.3 (11) | 0.9 |
a Data of lot Hu8246 were reproduced from Table 2 for comparison.
b Mean and percent coefficient of variance (n = 4).
PHH, plated human hepatocytes.