Effects of triptolide on pharmacokinetics of amlodipine in rats by using LC–MS/MS

Context: Triptolide and amlodipine are often simultaneously used for reducing urine protein excretion after renal transplantation in China clinics. Objective: This study investigated the effects of triptolide on the pharmacokinetics of amlodipine in male Sprague–Dawley rats. Materials and methods: The pharmacokinetics of amlodipine (1 mg/kg) with or without triptolide pre-treatment (2 mg/kg/day for seven days) were investigated using a sensitive and reliable LC–MS/MS method. Additionally, the inhibitory effects of triptolide on the metabolic stability of amlodipine were investigated using rat liver microsome incubation systems. Results: The results indicated that when the rats were pre-treated with triptolide, the C(max) of amlodipine increased from 13.78 ± 3.57 to 19.96 ± 4.56 ng/mL (p < 0.05), the T(max) increased from 4.04 ± 1.15 to 5.89 ± 1.64 h (p < 0.05), and the AUC(0–)(t) increased by approximately 104% (p < 0.05), which suggested that the pharmacokinetic behaviour of amlodipine was affected after oral co-administration of triptolide. Additionally, the metabolic half-life was prolonged from 22.5 ± 4.26 to 36.8 ± 6.37 min (p < 0.05) with the pre-treatment of triptolide. Conclusions: In conclusion, these results indicated that triptolide could affect the pharmacokinetics of amlodipine, possibly by inhibiting the metabolism of amlodipine in rat liver when they are co-administered.