Effect of naringenin on the pharmacokinetics of metoprolol succinate in rats

1. 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.
2. 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.
3. 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).
4. Compared to the metoprolol control group, the Cmax, AUC, and half-life (T1/2) of metoprolol increased in rats pre-treated with naringenin, while there was no significant change in Tmax. There is a significant decrease in clearance and volume of distribution.
5. The present study results revealed that naringenin significantly enhanced the Cmax, AUC, MRT, t1/2, and decreased the clearance of metoprolol possibly through the inhibition of CYP enzymes involved in the metabolism of metoprolol.