Abstract

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 C_max, AUC, and half-life (T_1/2) of metoprolol increased in rats pre-treated with naringenin, while there was no significant change in T_max. There is a significant decrease in clearance and volume of distribution.

5. The present study results revealed that naringenin significantly enhanced the C_max, AUC, MRT, t_1/2, and decreased the clearance of metoprolol possibly through the inhibition of CYP enzymes involved in the metabolism of metoprolol.

摘要

1. 本研究的目的是研究柚皮素（4,5,7-三羟基黄酮酮）对大鼠美托洛尔（细胞色素 P-450 3A4 (CYP3A4)、CYP2C9 和 CYP2D6 的底物）药代动力学的影响。

2. 雄性 Wistar 大鼠每天一次口服美托洛尔 (30 mg/kg) 和联合柚皮素 (25、50 和 100 mg/kg)，连续 15 天。

3. 在单剂量药代动力学 (PK) 研究 (SDS) 的第 1 天和多次给药 PK 研究 (MDS) 的第 15 天，使用反相高效液相色谱 (RP-HPLC) 测定美托洛尔的血浆浓度。

4. 与美托洛尔对照组相比，柚皮素预处理的大鼠的C _max、AUC 和半衰期（T _1/2）增加，而T _max没有显着变化。清除率和分布容积显着降低。

5. 本研究结果表明，柚皮素显著增强Ç_最大值， AUC，MRT，吨_1/2，以及可能通过CYP的抑制酶参与美托洛尔的代谢降低美托洛尔的清除。