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Effect of naringenin on the pharmacokinetics of metoprolol succinate in rats
Xenobiotica ( IF 1.3 ) Pub Date : 2021-06-28 , DOI: 10.1080/00498254.2021.1942311
Ravindra Babu Pingili 1 , Sridhar Vemulapalli 2 , Vijaya R Dirisala 3 , Surya Sandeep Mullapudi 4 , Yamini Gullapalli 4 , Naveen Babu Kilaru 4
Affiliation  

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 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.



中文翻译:

柚皮素对琥珀酸美托洛尔大鼠药代动力学的影响

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,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。

更新日期:2021-07-22
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