Pharmacokinetic interaction between diltiazem and morin, a flavonoid, in rats

Abstract

The present study aims to investigate the effect of morin, a flavonoid, on the pharmacokinetics of diltiazem and its active metabolite, desacetyldiltiazem, in rats. Pharmacokinetic parameters of diltiazem and desacetyldiltiazem were determined in rats after an oral administration of diltiazem (15 mg kg −1) to rats in the presence and absence of morin (1.5, 7.5 and 15 mg kg −1). Compared to the control given diltiazem alone, the C max and AUC of diltiazem increased by 30–120% in the rats co-administered with a 1.5 or 7.5 mg kg −1 of morin, while there was no significant change in T max and terminal plasma half-life ( T 1/2) of diltiazem in the presence of morin. Consequently, absolute and relative bioavailability values of diltiazem in the rats co-administered with morin were significantly higher ( p < 0.05) than those from the control group. Metabolite-parent AUC ratio in the presence of morin (7.5 mg kg −1) decreased by 30% compared to the control group, implying that coadministration of morin could be effective to inhibit the CYP3A4-mediated metabolism of diltiazem. In conclusion, the presence of morin significantly enhanced the oral exposure of diltiazem, suggesting that concurrent use of morin or morin-containing dietary supplement with diltiazem should require close monitoring for potential drug interactions.