Evaluation of Drug-diet interaction between Psidium guajava (Guava) fruit and Metoclopramide
Abstract
Studies have showed that phytochemicals present in fruit juices alter the oral bioavailability of drugs by inhibition of metabolising enzymes and transport proteins. The present study aimed to investigate the effect of Psidium guajava on the oral exposure of metoclopramide in rabbits. Pharmacokinetic parameters of metoclopramide were determined in rabbits following an oral (0.5mg/kg) administration of metoclopramide in the presence and absence of Psidium guajava (5mL/kg, given orally). Compared to the control group given metoclopramide alone, the combined use of Psidium guajava increased the oral exposure (AUC) of metoclopramide by 13% with a corresponding 177 % increase in Cmax and half-life (71%). Furthermore, Tmax decreased from 2h to 1h which might have contributed to the elevated plasma drug concentration in the first two hours in the presence of Psidium guajava. There was a significant increase in Cmax (177%) and Ka (207%) which could be attributed to enhanced absorption via inhibition of P-gp resulting to increased bioavailability of the drug. In contrast, there was a significant decrease in elimination rate (88%) and a decrease in clearance rate (17%) attributable to inhibitor of P450 enzymes (CYP2D6) by the phytochemical constituents. Psidium guajava enhanced the oral exposure of metoclopramide in rabbits likely by the inhibition of P-glycoprotein-mediated efflux during the intestinal absorption and inhibition of P450 enzyme system during metabolism, suggesting that the combined use of Psidium guajava or Psidium guajava-containing diet with metoclopramide may require close monitoring for potential drug–diet interactions.
Keywords: metoclopramide, Psidium guajava, diet–drug interaction, P-glycoprotein, P450 enzymes.
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