Influence of P-gp inhibitor on intestinal absorption of [14C]bepotastine and fexofenadine at distal region in rats
The absorption at the distal region of [14C]bepotastine and fexofenadine in the presence or absence of P-gp inhibitor was evaluated by the closed loop method. The data correspond to the intestinal absorption at the distal region within 30 min after injection to intestinal loop (8 cm). Each value represents the mean ± S.E.M. of three animals. The values in parentheses represent the ratio of the apparent absorption rate constant (ka) by [14C]bepotastine (1 μM), fexofenadine (370 μM), and [14C]mannitol (2 μM).
Condition | Absorption Rate | ka |
|---|---|---|
| % of dose | h-1 | |
| [14C]Bepotastine (1 μM) | 10.9 ± 1.2 | 0.26 ± 0.03 (1.00) |
| [14C]Bepotastine (20 mM) | 38.3 ± 2.0a | 0.97 ± 0.07a (3.79) |
| [14C]Bepotastine (1 μM) + cyclosporin A (50 μM) | 59.7 ± 1.4 | 1.89 ± 0.07a (7.41) |
| [14C]Bepotastine (1 μM) + verapamil (10 mM) | 62.7 ± 2.8a | 1.98 ± 0.15a (7.77) |
| [14C]Bepotastine (1 μM) + quinidine (10 mM) | 46.0 ± 2.5a | 1.24 ± 0.09a (4.85) |
| Fexofenadine (370 μM) | 4.2 ± 1.2 | 0.09 ± 0.03 (1.00) |
| Fexofenadine (370 μM) + cyclosporin A (50 μM) | 17.9 ± 0.9a | 0.40 ± 0.02a (4.58) |
| Fexofenadine (370 μM) + verapamil (10 mM) | 13.0 ± 3.2 | 0.28 ± 0.08a (3.27) |
| [14C]Mannitol (1 μM) | 3.5 ± 1.1 | 0.07 ± 0.03 |
↵ a Statistical difference of the absorption rate (% of dose) and the apparent absorption rate constant, ka, in the presence of excessive bepotastine and P-gp inhibitors was assessed by Student's t test (P < 0.05).