Drug-Phytochemical Interaction: In vitro Investigation of the Effects of <i>Aframomum melegueta</i> Seed Extract on Acetaminophen and Amlodipine Absorption

Abstract

The concomitant use of herbal preparations by patients presenting in health facilities may impact the pharmacokinetic processes of orthodox drugs. This study was aimed at evaluating the impact of phytochemicals of Aframomum melegueta (AM) seeds on the bioavailability of acetaminophen (N-acetyl-p-aminophenol) and amlodipine. The everted intestinal sac model was used to assess the transfer of Acetaminophen and amlodipine across the intestinal wall. A portion of the small intestine was excised, everted, filled with Tyrode solution with both ends ligated to make a closed loop, and immersed in a beaker containing a concentration of the test drug either alone or in the presence of AM seed extract (AMSE). After a time to achieve transfer equilibrium, the everted tissues were removed, and the concentration of the test drug was determined in these serosal fluids to assess transfer efficiency. The study showed that AM seed extract severely inhibited the intestinal transfer of acetaminophen by as much as 82.4% while amlodipine transfer was enhanced by up to 94.5%. Serosal concentrations of acetaminophen in the absence and presence of AMSE were 7.62 ± 0.95 µg ml-1 and 1.34 ± 0.96 µg ml-1 (P<0.001), respectively while that for amlodipine were 2.54 ±1.03 µg ml-1 and 4.94 ± 0.739 µg ml-1 respectively. The depression of APAP transfer was suggested to be due to chemical interaction with nitric oxide produced by the interaction of the phytoestrogens in the extract on the GPCR-bound estrogen receptor. This type of interaction may have serious health consequences.