Effects of Danshen tablets on pharmacokinetics of amlodipine in rats

Abstract

Context: Danshen tablets (DST), an effective traditional Chinese multi-herbal formula, are often combined with amlodipine (ALDP) for treating coronary heart disease. Objective: This study investigated the effects of DST on the pharmacokinetics of ALDP and the potential mechanism. Materials and methods: The pharmacokinetics of ALDP (1 mg/kg) in male Sprague–Dawley rats (n = 6), with or without pretreatment of DST (100 mg/kg for 7 d), were investigated using LC-MS/MS. The effects of DST on the metabolic stability of ALDP were also investigated using rat liver microsomes (RLM). Results: The results indicated that Cmax (16.25 ± 2.65 vs. 22.79 ± 2.35 ng/ml), AUC(0–t) (222.87 ± 59.95 vs. 468.32 ± 69.87 n gh/ml), and t1/2 (10.60 ± 1.05 vs. 14.15 ± 1.59 h) decreased significantly when DST and ALDP were co-administered, which suggested that DST might influence the pharmacokinetic behaviour of ALDP when they are co-administered. The metabolic stability of ALDP was also decreased (23.6 ± 4.7 vs. 38.9 ± 5.2) with the pretreatment of DST. Discussion and conclusions: This study indicated that DST could accelerate the metabolism of ALDP in RLM and change the pharmacokinetic behaviours of ALDP. Accordingly, these results showed that the herb–drug interaction between DST and ALDP might occur when they were co-administered. Therefore, the clinical dose of ALDP should be increased when DST and ALDP are co-administered.

Keywords

• herb–drug interaction
• cyp3a4
• metabolism