Effects of triptolide on pharmacokinetics of fenofibrate in rats and its potential mechanism

Abstract

Triptolide and fenofibrate are often used together for the treatment of nephrotic syndrome in Chinese clinics.This study investigates the effects of triptolide on the pharmacokinetics of fenofibrate in rats and it potential mechanism.The pharmacokinetics of fenofibrate (20 mg/kg) with or without triptolide pretreatment (2 mg/kg/day for seven days) were investigated. Additionally, the inhibitory effects of triptolide on the metabolic stability of fenofibrate were investigated using rat liver microsome incubation systems.The results indicated that the Cmax (35.34 ± 7.52 vs. 30.43 ± 6.45 μg/mL), t1/2 (6.17 ± 1.15 vs. 4.90 ± 0.82 h) and AUC(0–t) (468.12 ± 35.84 vs. 416.35 ± 32.68 mg h L−1) of fenofibric acid decreased significantly (p < .05). The Tmax of fenofibric acid increased significantly (p < .05) from 5.12 ± 0.36 to 6.07 ± 0.68 h. Additionally, the metabolic stability of fenofibrate was prolonged from 35.8 ± 6.2 to 48.6 ± 7.5 min (p < .05) with the pretreatment of triptolide.In conclusion, these results indicated that triptolide could affect the pharmacokinetics of fenofibric acid, possibly by inhibiting the metabolism of fenofibrate in rat liver when they were co-administered.