Effects of Danshen tablets on pharmacokinetics of atorvastatin calcium in rats and its potential mechanism

Abstract

Context: Danshen tablets (DST), an effective traditional Chinese multi-herbal formula, are often combined with atorvastatin calcium (AC) for treating coronary heart disease in the clinic.Objective: This study investigated the effects of DST on the pharmacokinetics of AC and the potential mechanism.Materials and methods: The pharmacokinetics of AC (1 mg/kg) with or without pretreatment of DST (100 mg/kg) were investigated using LC-MS/MS. The effects of DST (50 μg/mL) on the metabolic stability of AC were also investigated using rat liver microsome incubation systems.Results: The results indicated that Cmax (23.87 ± 4.27 vs. 38.94 ± 5.32 ng/mL), AUC(0–t) (41.01 ± 11.32 vs. 77.28 ± 12.92 ng h/mL), and t1/2 (1.91 ± 0.18 vs. 2.74 ± 0.23 h) decreased significantly (p < 0.05) when DST and AC were co-administered, which suggested that DST might influence the pharmacokinetic behavior of AC when they are co-administered. The metabolic stability (t1/2) of AC was also decreased (25.7 ± 5.2 vs. 42.5 ± 6.1) with the pretreatment of DST.Discussion and conclusions: This study indicated that the main components in DST could accelerate the metabolism of AC in rat liver microsomes and change the pharmacokinetic behaviors of AC. So these results showed that the herb-drug interaction between DST and AC might occur when they were co-administered. Therefore, the clinical dose of AC should be adjusted when DST and AC are co-administered.

Effects of Ginkgo leaf tablets on the pharmacokinetics of atovastatin in rats

“…Previous studies (Sun et al. 2018) have also reported that drugs or herbs could affect the pharmacokinetics of AC through affecting the activity of CYP3A4 enzyme.…”

“…2016; Sun et al. 2018). Group B was pre-treated with GLT solutions by oral gavage at a dose of 80 mg/kg/day for 10 days before the administration of AC, and then AC were orally administered to rats by oral gavage at a dose of 1 mg/kg.…”

“…The determination of AC was performed as previously reported by Sun et al. (2018). The analysis was performed on an Agilent 1290 series liquid chromatography system (Agilent Technologies, Palo Alto, CA, USA).…”

In vivo Absorption Study of Solid Dispersion Containing Atorvastatin Calcium in Human Volunteers

“…A clear change was observed in the AUC 0 -60h and AUC 0-∞ between the different formulae. In ATV-SD tablets the mean AUC (0-60) was found to increased from 63.54 ng.hr/ ml to 92.35 ng.h/ml, in addition the AUC(0-∞) was increased from 65.40 ng.hr/ ml to 95.73 ng.hr/ml , which indicated that the pharmacological activities of ATV may be increased 24 . The mean elimination half-life (T1/2) and elimination rate constant (K) were 4.68 hr and 0.15hr -1 , respectively in ATV-SD tablets .…”

Improved Understanding of the High Shear Wet Granulation Process under the Paradigm of Quality by Design Using Salvia miltiorrhiza Granules

“…It has been widely applied clinically in the treatment of obstructive cerebrovascular diseases [21], atherosclerosis [22], coronary heart disease [23], and other cardiovascular diseases [24,25]. Furthermore, many different preparations of S. miltiorrhiza can be found, including compounded danshen dripping pills [26], danhong injection [27], danshen injection [28], danshen tablets [29], and danshen granules [30]. Moreover, S. miltiorrhiza extract is a high-value raw pharmaceutical material commonly used in Chinese patented medicine production.…”