Effect Of epigallocatechin-3-gallate on the pharmacokinetics of amlodipine in rats

Abstract

This study investigates the effect of epigallocatechin-3-gallate (EGCG), a major ingredient of green tea, on the pharmacokinetics of amlodipine in rats. The pharmacokinetics of orally administered amlodipine (1 mg/kg) with or without EGCG pretreatment (30 mg/kg/day for 10 days) were investigated. Plasma concentrations of amlodipine were determined by using a sensitive and reliable liquid chromatography with tandem mass spectroscopy (LC-MS/MS) method. The effects of EGCG on the metabolic stability of amlodipine were investigated by using rat liver microsome incubation systems. The results indicated that when the rats were pretreated with EGCG, the C_max of amlodipine increased from 16.32 ± 2.57 to 21.44 ± 3.56 ng/mL (p < 0.05), the T_max decreased from 5.98 ± 1.25 to 4.01 ± 1.02 h (p < 0.05), and the AUC_0-t increased from 258.12 ± 76.25 to 383.34 ± 86.95 μg h L^-1 (p < 0.05), which suggested that the pharmacokinetic behavior of amlodipine was affected after oral co-administration of EGCG. Additionally, the metabolic half-life was prolonged from 31.3 ± 5.6 to 52.6 ± 7.9 min (p < 0.05) with the pretreatment of EGCG. It can be speculated that the drug-drug interaction between EGCG and amlodipine might occur, which might have resulted from the metabolism inhibition of amlodipine by EGCG when they were co-administered.

Keywords: Drug–drug interaction; EGCG; LC-MS/MS; amlodipine; pharmacokinetics.