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Abstract

FRUIT/VEGETABLE–DRUG INTERACTIONS: PHARMACOKINETIC ASSAY WITH A CYP3A4 SUBSTRATE

Cecilia Nwadiuto Amadi* and Etoroabasi Edem Peters

ABSTRACT

Important health benefits of complex mixtures of phytochemicals in fruits and vegetables have been established. However, these phytochemicals have been shown to influence the pharmacological activity of drugs by modifying activities of key metabolizing enzyme systems, specifically the cytochrome P450 enzymes. Felodipine, an antihypertensive agent, has been identified as a substrate for CYP3A4.Carica papaya (pawpaw fruit) and Telfairia occidentalis(ugu/pumpkin vegetable) are common staple fruit and vegetable regularly consumed in Nigeria. However, the potential fruit/vegetable-drug interactions between felodipine and pawpaw/pumpkin are unknown. The objective of this study was to investigate the effects of pawpaw juice and pumpkin (ugu) vegetable extract on the pharmacokinetics of felodipine in rats. The pharmacokinetic profiles of orally administered felodipine (10 mg/kg) in the absence and presence of pawpaw juice (10 mL/kg) /pumpkin (ugu) extract (10 mL/kg) were investigated in rats. There was a significant (p<0.05) reduction in AUC and Ka while the clearance rate increased on concurrent administration with pawpaw and pumpkin extract. The AUC values for the groups that received pawpaw and pumpkin (ugu) extract were 84% and 48% lower than the group that received felodipine alone. The elimination rate in the group of rats that received both felodipine and pawpaw was 29% lower than the corresponding values obtained in the group that received felodipine alone. A 43% increase in clearance rate was observed in the group that received felodipine and ugu (pumpkin) extract as compared to the group that received felodipine alone while clearance rate was increased to about 548% in the group that received pawpaw juice. Reduction in felodipine bioavailability was moderate in the group administered with pumpkin extract compared to the group that received pawpaw juice. These findings support activation or induction of CYP3A4-mediated pre-systemic felodipine metabolism as the most likely mechanism. This fruit juice–drug interaction rat model may be useful in prediction of potential food–drug interactions in humans.

Keywords: fruit/vegetable-drug interactions, pharmacokinetics, bioavailability, enzyme induction.


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