Effect of Morin on Pharmacokinetics of Prasugrel in Rats & In Vitro Metabolic Stability Followed by UPLC Method

The aim of present study was to investigate the effect of Morin on the pharmacokinetics of Prasugrel, a substrate of P-glycoprotein (P-gp) and Cytochrome 3A (CYP3A), in rats, and metabolic stability (high throughput) studies using human liver microsomes in UPLC. For pharmacokinetics studies, Male wistar rats were pretreated with Morin (10 mg/kg) for 1 week and on the last day, a single dose of Prasugrel (1 mg/ kg) was given orally. In another group, both morin and Prasugrel were co-administered to evaluate the acute effect of morin on Prasugrel. The control group received oral distilled water for 1 week and administered with Prasugrel on the last day. As Morin is a known inhibitor of PGlycoprotein (P-gp) and CYP 3A, it was expected to improve the bioavailability of Prasugrel. Surprisingly, the area under the concentration–time curve and peak plasma concentration relative to control of Prasugrel were 1.50and 1.45fold, respectively, greater in the morin-pretreated group. However, co-administration of morin had no significant effect on these parameters. Prasugrel dosages should be accustomed to avoid concomitant for potential drug interaction when Prasugrel is used clinically in combination with morin and morin-containing dietary supplements. Apart from aforementioned merits, the results of this study are further confirmed by clinical trials.