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 C(max) (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 t(1/2) (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.