Effect of naringenin on the pharmacokinetics of metoprolol succinate in rats.

The aim of the present study was to investigate the effect of naringenin (4,5,7-trihydroxy flavonone) on the pharmacokinetics of metoprolol, a substrate of Cytochrome P-450 3A4 (CYP3A4), CYP2C9, and CYP2D6 in rats.Male Wistar rats were treated orally with metoprolol (30 mg/kg) alone and in combination with naringenin (25, 50, and 100 mg/kg) once daily for 15 consecutive days.The plasma concentrations of metoprolol were determined using Reverse Phase-High Performance Liquid Chromatography (RP-HPLC) on the 1st day in single-dose pharmacokinetic (PK) study (SDS) and on the 15th day in multiple dosing PK studies (MDS).Compared to the metoprolol control group, the , AUC, and half-life () of metoprolol increased in rats pre-treated with naringenin, while there was no significant change in . There is a significant decrease in clearance and volume of distribution.The present study results revealed that naringenin significantly enhanced the AUC, MRT, , and decreased the clearance of metoprolol possibly through the inhibition of CYP enzymes involved in the metabolism of metoprolol.