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  • Title: Effects of cucurbitacin e, a tetracyclic triterpene compound from Cucurbitaceae, on the pharmacokinetics and pharmacodynamics of warfarin in rats.
    Author: Ding T, Zhang Y, Chen A, Tang Y, Liu M, Wang X.
    Journal: Basic Clin Pharmacol Toxicol; 2015 May; 116(5):385-9. PubMed ID: 25250504.
    Abstract:
    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 200 μg/kg, i.p.) decreased warfarin clearance (28-32%), increased the area under the curve (AUC0-∞; 55-62%) and prolonged plasma half-life (t1/2; 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.
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