Pharmacokinetic interaction between febuxostat and morin in rats.

Background: Due to wide consumption of flavonoids in the dietary supplement, and an imperative role of CYPs and P-glycoprotein inhibition in drug disposition. So there is increasing scientific interest in drug-flavonoid interactions.

Objective: The present study aims to investigate the effect of morin, a flavonoid, on the pharmacokinetics of febuxostat in rats.

Methods: A simple ultra-performance liquid chromatography method has been developed for the calculation of febuxostat in 100 µl rat plasma using febuxostat D7 as an internal standard (IS). The assay procedure involved a single-step, liquid-liquid extraction of febuxostat and IS from plasma with methanol. Pharmacokinetic parameters of febuxostat were determined in rats after an oral administration of febuxostat (5 mg/kg) to rats in the control, coadministered and pretreated groups of morin (10 mg/kg).

Results: Compared to the control rats given febuxostat alone, the Cmax and AUC of febuxostat increased by 18 - 20 and 47 - 50%, respectively, in rats pretreated with morin. The plasma half-life (t1/2) of the pretreated group is increased by 2.5-fold compared with the control group. Consequently, relative bioavailability values of febuxostat in the rats pretreated with morin were significantly higher (p < 0.05) than those from the control and coadministered groups. Increased bioavailability indicates that the presence of morin could be effective in inhibiting CYP1A1, CYP1A2 and CYP3A4-mediated metabolism and/or effective in inhibiting P-glycoprotein-mediated cellular efflux of febuxostat.

Conclusion: The presence of morin significantly enhanced the oral exposure of febuxostat, suggesting that concurrent use of morin or morin-containing dietary supplements with febuxostat should be verified to avoid drug-flavonoid interactions.