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 of amlodipine increased from 13.78 ± 3.57 to 19.96 ± 4.56 ng/mL (p < 0.05), the T increased from 4.04 ± 1.15 to 5.89 ± 1.64 h (p < 0.05), and the AUC 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.