Effect of hesperetin on the pharmacokinetics of metoprolol succinate in rats

Abstract Background Metoprolol is a substrate of CYP3A4, 2B6, CYP2D6, CYP2C9, and p -glycoprotein ( -gp). Hesperetin was reported as an inhibitor cytochrome P-450 (CYP) enzymes -gp. The objective this study to investigate the effect hesperetin on pharmacokinetics metoprolol in rats vitro models. In vivo studies, male Wistar were treated with (30 mg/kg) once day for 15 consecutive days alone combination (25, 50, 100 mg/kg). Blood samples withdrawn from tail vein 1st single-dose pharmacokinetic 15th repeated-dose study. incubated presence or absence traditional -gp inhibitors using rat-everted gut sacs. Reverse phase-high-performance liquid chromatography (RP-HPLC) used determine amounts plasma (RP-HPLC). Results C max , AUC, half-life t 1/2 ) significantly increased by twofold compared group pre-treated hesperetin. clearance volume distribution both decreased significantly. transport dramatically quinidine (standard inhibitor) Conclusion present results revealed that absorption everted sacs might be due inhibition CYP