Contribution of OATP2 and OATP8 to the hepatic uptake of pitavastatin and E217βG determined by the relative expression level
Hepatocyte Lot | Ratio of Expression Levela | Estimated Clearanceb | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Hepatocyte Transporter | E-sul | CCK-8 | Pitavastatin | E217βG | ||||||||||
| Rexp,OATP2 | Rexp,OATP8 | OATP2 | OATP8 | OATP2 | OATP8 | OATP2 | OATP8 | |||||||
| μl/min/106 cells | ||||||||||||||
| OCF | 2.90 | 1.21 | 383 | 32.3 | 222 | 37.0 | 45.8 | 2.80 | ||||||
| 85.7% | 14.3% | 94.2% | 5.76% | |||||||||||
| 094 | 1.58 | 0.930 | 208 | 24.8 | 121 | 28.4 | 24.9 | 2.15 | ||||||
| 80.9% | 19.1% | 92.1% | 7.95% | |||||||||||
| ETR | 0.89 | 0.737 | 117 | 19.7 | 68.1 | 22.6 | 14.0 | 1.71 | ||||||
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|
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| 75.1% | 24.9% | 89.2% | 10.8% | ||||||
↵ a Ratio of the expression level was determined by the intensity of the specific band in the crude membrane prepared from human hepatocytes (per 106 cells) divided by that in the crude membrane from transporter-expressing cells (per milligram) in Western blot analysis.
↵ b The second line entry under “Estimated Clearance” shows the percentage of the OATP2- or OATP8-mediated uptake clearance relative to the sum of the estimated clearance mediated by OATP2 and OATP8. The details of this estimation are described under Materials and Methods.