Fractional metabolite and effective permeability of indinavir as a function of luminal concentration of indinavir, determined in rat upper jejunal in situ perfusion
| Luminal Concentration of Indinavir | ||||||
|---|---|---|---|---|---|---|
| 1 μM | 10 μM | 50 μM | ||||
| Jejunum | Ileum | Jejunum | Ileum | Jejunum | Ileum | |
| P eff of indinavir × 106(cm/s) | 35.90 (10.52) | 57.83 (13.55) | 9.00 (1.50) | 77.50 (7.00) | ||
| Fractional metabolite (%) | 87.90 (14.30) | 0 | 65.78 (19.02) | 0 | 35.84 (11.59) | 0 |
Perfusion solutions are MES buffer containing 1 μM, 10 μM, and 50 μM indinavir, respectively, and were at pH 6.5 except for 50 μM indinavir solution, the pH of which was readjusted to 6.3 to reach higher solubility. Fractional metabolite was calculated as percentage of M6 over total luminal loss of parent drug, and the effective permeability of indinavir was determined based on total loss of drug from lumen (for details see Materials and Methods).