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 that 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 (P-gp)] on the intestinal absorption of ABL by comparing the changes in the absorption rate constant (k_ap) of ABL.

In situ intestinal perfusion was conducted in healthy male Wistar albino 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.

The absorption study showed that k_ap of ABL in the first group was 0.47±0.045 h-¹. In the third group k_ap increased 3-fold (1.37±0.031 h-¹); however, the second group showed a statistically insignificant change in k_ap (0.39±0.076 h-¹).

The results revealed that VER at a concentration of 400 μg/mL has a pronounced effect on the absorption kinetics of ABL (increased k_ap). This could be linked to the inhibition of P-gp, which is considered a contributing factor in low bioavailability of ABL.