In Situ Absorption Study of Acebutolol by Modulating P-glycoprotein with Verapamil in Rats

Acebutolol HCl (ABL) is a selective β-adrenergic receptor blocking agent which is preferably administered by the oral route despite its low bioavailability (30-50 %). The purpose of this study was to evaluate the effect of verapamil HCl (VER) (as P-glycoprotein inhibitor) on the intestinal absorption of ABL by comparing the changes in the absorption rate constant (kap) of ABL. Materials and Methods: In situ intestinal perfusion technique was conducted in healthy Wistar albino male rats to study the absorption phase of ABL. Eighteen rats were divided into three groups. The first group (the control group) was perfused with ABL alone (260 μg/mL). The second and third groups were perfused with ABL (260 μg/mL) in combination with VER at different concentrations (200 and 400 μg/mL, respectively). The analysis was performed using a simple, rapid and validated spectroscopic method. Results: The absorption study showed that kap of ABL in the first group was 0.47 ± 0.045 h-1. In the third group kap increased 3 folds (1.37 ± 0.031 h-1), however, the second group showed statistically insignificant change in kap (0.39 ± 0.076). Conclusion: Results revealed that VER at concentration 400 μg/mL has a pronounced effect on the absorption kinetic of ABL (increased kap) which could be linked to the inhibition of P-gp that considered as a contributed factor of low bioavailability of ABL.