关键词: 中药制剂, 氯吡格雷, 活性代谢产物, 药动学, 中西药相互作用

Abstract:

In the present study, we aimed to examine the effects of Rong Shuan capsule, Xue Zhi Kang capsule, Xin Yuan capsule and Songling Xue Mai Kang capsule on the pharmacokinetics of clopidogrel active metabolite (CAM). The traditional Chinese medicines (TCMs) Rong Shuan capsule, Xue Zhi Kang capsule, Xin Yuan capsule and Songling Xue Mai Kang capsule are widely used to treat cardiovascular disease in China. They are often prescribed in combination with clopidogrel, a common anti-platelet Western drug. We investigated the influence of the four TCMs on CAM pharmacokinetics following administration at human dose in rats. Pharmacokinetic parameters were determined following oral (PO) administration of clopidogrel (7.5 mg/kg) with or without Rong Shuan capsule (75 mg/kg, PO), Xue Zhi Kang capsule (60 mg/kg, PO), Xin Yuan capsule (120 mg/kg, PO), or Songling Xue Mai Kang capsule (150 mg/kg, PO). Compared with the animals in the control group, Xue Zhi Kang capsule significantly decreased the area under the plasma concentration-time curve (AUC0-t) of the CAM derivative by 25.4%. However, the t1/2 and Vz/F of CAM derivative were significantly increased by 43.6% and 70.7%, respectively. It was also observed that the pharmacokinetic parameters were altered in groups pretreated with Rong shuan capsule, Xin yuan capsule or Songling Xue mai kang capsule compared with the control group, but not significant. This study indicated that Xue Zhi Kang capsule had an effect on the formation and metabolism of CAM. Therefore, in the beginning of co-administration of Xue Zhi Kang capsule and clopidogrel, the anti-platelet efficacy might be compromised because of the decreased formation of CAM. Otherwise, long-time co-administration might lead to side effects by the prolongation of the t1/2 and Vz/F increase of CAM.

Key words: TCMs, Clopidogrel, Active metabolite, Pharmacokinetics, Herb-drug interaction