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.
Highlights
Atorvastatin, a synthetic and lipophilic statin, inhibits 3-hydroxy3-methylglutaryl coenzyme A (HMG-CoA) reductase, the ratelimiting enzyme in cholesterol biosynthesis (Dybro et al 2016; Eng et al 2016; Cruz-Correa et al 2017; Dennison et al 2017)
This study investigates the effects of Danshen tablets (DST) on the pharmacokinetics of atorvastatin calcium (AC) in rats, and to clarify the herb-drug interaction potential between DST and AC
The results indicated that the Cmax (23.87 ± 4.27 vs. 38.94 ± 5.32 ng/mL), area under the plasma concentration-time curve (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 when DST and AC were co-administered, which suggested that DST might influence the pharmacokinetic
Summary
Atorvastatin, a synthetic and lipophilic statin, inhibits 3-hydroxy3-methylglutaryl coenzyme A (HMG-CoA) reductase, the ratelimiting enzyme in cholesterol biosynthesis (Dybro et al 2016; Eng et al 2016; Cruz-Correa et al 2017; Dennison et al 2017). Growing experimental evidence shows the cholesterol-independent pleiotropic effects of this drug, including protection against Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, depression, convulsion, peripheral neuropathy and intracerebral hemorrhage (Roth et al 2016; Shu et al 2016; Wang et al 2016). Except pravastatin, are metabolized by the cytochrome P450 (CYP) enzymes (Wei and Zhang 2015; Hsiao et al 2016). Itraconazole has been shown to increase the area under the plasma concentration-time curve (AUC) of atorvastatin acid and lactone by three- and four-fold, respectively (Higgins et al 2014; Dybro et al 2016)
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