Inhibitory Effect of Apigenin on Pharmacokinetics of Venlafaxine in vivo and in vitro

Pharmacology. 2015;96(3-4):118-23. doi: 10.1159/000437056. Epub 2015 Jul 22.

Abstract

Objective: This study was conducted to investigate the effects of orally administered apigenin on the pharmacokinetics of venlafaxine (VEN) in rats and on the metabolism of VEN in human and rat liver microsomes in vitro.

Methods: Ten healthy male SD rats were randomly divided into 2 groups: A group (control group), B group (a single dose of 250 mg/kg apigenin). A single dose of 20 mg/kg VEN was administered orally 30 min after administration of apigenin (250 mg/kg). VEN plasma levels were measured by HPLC with fluorescence detection, and pharmacokinetic parameters were calculated by DAS 3.0 software.

Results: The single dose of 250 mg/kg apigenin significantly increased the AUC0-t of VEN by 40.9% (p < 0.05) and obviously increased the peak plasma concentration (Cmax) of VEN (p < 0.05). Furthermore, apigenin showed inhibitory effect on human and rat microsomes and the IC50 of apigenin was 58.37 and 25.73 μmol/l, respectively.

Conclusions: Our results indicated that an intake of apigenin could increase VEN plasma levels and some of its pharmacokinetic parameters (AUC, Tmax). Thus, more attention should be paid when VEN was administrated combined with apigenin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antidepressive Agents, Second-Generation / pharmacokinetics*
  • Apigenin / pharmacology*
  • Area Under Curve
  • Drug Interactions
  • Half-Life
  • Humans
  • In Vitro Techniques
  • Male
  • Microsomes, Liver / drug effects
  • Microsomes, Liver / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Venlafaxine Hydrochloride / antagonists & inhibitors
  • Venlafaxine Hydrochloride / pharmacokinetics*

Substances

  • Antidepressive Agents, Second-Generation
  • Venlafaxine Hydrochloride
  • Apigenin