EFFECT OF PINEAPPLE (ANANAS COMOSUS) AND UZIZA (PIPER GUINEENSE) EXTRACTS ON FEXOFENADINE BIOAVAILABILITY: POSSIBLE ROLE OF P-GLYCOPROTEIN (P-GP) AND ORGANIC ANION TRANSPORTING POLYPEPTIDES (OATPs)

Abstract

The consumption of fruits/vegetables as sources of nutrients is important for healthy growth and development of the body. When used in combination with certain drugs, there is a tendency for interaction to occur, which is due to different bioactive phytochemical constituents which alter the activities of drugs transporters (efflux and influx transporters) and metabolizing enzymes, resulting to deviations in the expected pharmacological activity of the drug. The present study was aimed to investigate the effect of uziza (Piper guineense) and pineapple (Ananas comosus) extracts on the oral exposure of fexofenadine in rats. Pharmacokinetic parameters of fexofenadine were determined in rats following an oral (10 mg/kg) administration of fexofenadine in the presence and absence of pineapple and uziza extracts (10 mL/kg given orally) compared to the control group given fexofenadine alone. The combined use of pineapple decreased the oral exposure (AUC)of fexofenadine by 47% while uziza extract increased the oral exposure (AUC) of fexofenadine by 31% as compared to the group that received fexofenadine alone (control group). There was a reduction in peak plasma concentration of fexofenadine when co-administered with pineapple and uziza by 3% and 61% respectively compared to control. The reduction is indicative of delayed absorption by phytochemical constituents of Piper guineense (uziza) and pineapple juice extracts. A 10% decrease in clearance rate was observed for the group that received fexofenadine and pineapple extract as compared to the group that received fexofenadine alone while clearance rate was increased to about 56% in the group that received uziza extract. An increase in half life was observed for the group that received pineapple while a decrease was observed for the group that received uziza as compared to control respectively. In conclusion, pineapple juice significantly enhanced the oral exposure of fexofenadine in rats likely by the inhibition of P-glycoprotein-mediated cellular efflux while uziza extract reduced fexofenadine oral exposure by inhibition of organic anion transporting polypeptides (OATPs) during the intestinal absorption suggesting that the combined use of pineapple or uziza- containing diet with fexofenadine may require close monitoring for potential drug–diet interactions.