Prediction of intestinal and hepatic first-pass metabolism of indinavir in control and DEX-treated rats (mean ± S.D., n = 4)
| Rat | Intestine | Liver | ||||
|---|---|---|---|---|---|---|
| Intrinsic clearance5-a | Predicted EG | Observed EG5-b | Intrinsic clearance5-a | Predicted EH | Observed EH5-c | |
| ml/min/kg | % | ml/min/kg | % | |||
| Control | 0.50 ± 0.14 | 0.98 ± 0.28 | 6.0 ± 3.0 | 166 ± 75 | 45 ± 10 | 65 ± 19 |
| DEX-treated | 1.87 ± 1.0 | 3.6 ± 2.0 | 34 ± 13 | 1403 ± 93 | 87 ± 8 | 82 ± 18 |
↵5-a The intrinsic clearance values were scaled up from the in vitro Vmax/Km values with the knowledge of the yield of microsomal protein and organ weight.
↵5-b The observed EG was determined using the in situ intestinal loop technique.
↵5-c The observed EH was determined by comparing the drug concentrations in the systemic circulation during portal and femoral vein infusion of indinavir.