Effects of Cucurbitacin E, a Tetracyclic Triterpene Compound from Cucurbitaceae, on the Pharmacokinetics and Pharmacodynamics of Warfarin in Rats
Effects of Cucurbitacin E, a Tetracyclic Triterpene Compound from Cucurbitaceae, on the Pharmacokinetics and Pharmacodynamics of Warfarin in Rats
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DOI：
10.1111/bcpt.12329
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发表时间：
2015-05-01
影响因子：
3.1
通讯作者：
Wang, Xin
中科院分区：
文献类型：
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作者：
Ding, Tonggui;Zhang, Yuanjin;Wang, Xin
本研究首先考察了葫芦科四环三萜化合物葫芦素E(CuE)对模型细胞色素P2 C探针底物华法林在大鼠体内的药代动力学(PK)和药效学(PD)的影响。在PK研究中，采用高效液相色谱法测定血样中华法林的浓度，并用非隔室方法分析PK参数。在PD研究中，通过凝血酶原试剂测定每个样本点的血浆凝血酶原时间(PT)。CUE处理(50、100和200g/kg，i.p)华法林清除率降低(28-32%)，曲线下面积增加(AUC(0-)；55-62%)，血浆半衰期延长(t(1/2)；58-72%)。同时，在有CUE存在的情况下，华法林(PTmax)的抗凝作用也明显增强。这些数据表明，CUE影响了华法林的PK和PD，这些作用可能是由于CUE抑制了CYP2C的活性。因此，在将含有CUE的草药产品与由CYP2C酶代谢的药物一起使用时，应进行仔细的监测。
This study firstly investigated the effects of cucurbitacin E (CuE), a tetracyclic triterpene compound from Cucurbitaceae, on the pharmacokinetics (PK) and pharmacodynamics (PD) of warfarin, a model CYP2C probe substrate, in the rat. In PK studies, the concentration of warfarin in blood samples was determined by HPLC-DAD, and the PK parameters were analysed using non-compartmental methods. In PD studies, the prothrombin time (PT) in blood plasma at each sample point was measured via thromboplastin reagents. CuE treatment (50, 100 and 200g/kg, i.p.) decreased warfarin clearance (28-32%), increased the area under the curve (AUC(0-); 55-62%) and prolonged plasma half-life (t(1/2); 58-72%). At the same time, the anticoagulation effect of warfarin (PTmax) was also significantly increased in the presence of CuE. These data demonstrated that CuE affected the PK and PD of warfarin, and these effects may be due to the inhibition of CYP2C activity by CuE. Hence, careful monitoring should be carried out during concomitant use of herbal products containing CuE with drugs that are metabolized by CYP2C enzymes.