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首页> 外文期刊>Canadian Journal of Physiology and Pharmacology >Reversal of P-glycoprotein-mediated multidrug resistance and pharmacokinetics study in rats by WYX-5
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Reversal of P-glycoprotein-mediated multidrug resistance and pharmacokinetics study in rats by WYX-5

机译：逆转对糖蛋白介导的多药抗性和药代动力学研究WYX-5

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摘要

Multidrug resistance (MDR) is one of the major obstacles confronted in cancer chemotherapy; this obstacle is mainly due to the overexpression of P-glycoprotein (P-gp). Co-administration of anticancer drugs and P-gp inhibitors is a promising approach to overcome MDR. WYX-5, a novel P-gp inhibitor, shows a notable reversal effect with low cytotoxicity in vitro. In this paper, the reversal mechanism and safety of the MDR modulator WYX-5 were explored in vitro, and evaluated for its pharmacokinetics and effects on adriamycin (ADM) metabolism in vivo. The results suggest that WYX-5 is a potent P-gp inhibitor with EC50 in nanomole range (EC50 = 204.3 +/- 20.2 nmol.L-1), relative safety (therapeutic index = 446.4), which performs as a substrate of P-gp and retrains its function. Further, WYX-5 (5 mg.kg(-1)) had relatively ideal pharmacokinetic properties (T-1/2 = 6.448 h, F = 96.05%) without interactions with ADM metabolism in vivo. In conclusion, WYX-5 may be a promising candidate for MDR cancer combined-chemotherapy research.
机译：多药耐药性（MDR）是癌症化疗中面临的主要障碍之一;该障碍主要是由于P-糖蛋白（P-GP）的过表达。抗癌药物和P-GP抑制剂的共同施用是克服MDR的有希望的方法。 WYX-5新型P-GP抑制剂，表明，体外具有低细胞毒性的显着反转效果。本文在体外探讨了MDR调节剂WYX-5的逆转机制和安全性，并评估其药代动力学和对体内adriamycin（ADM）代谢的影响。结果表明，WYX-5是一种有效的P-GP抑制剂，其具有EC50的纳米摩尔（EC50 = 204.3 +/- 20.2 Nmol.L-1），相对安全（治疗指数= 446.4），其作为P的基材进行-GP并删除其功能。此外，WYX-5（5mg.kg（-1））具有相对理想的药代动力学性质（T-1/2 = 6.448h，f = 96.05％），而不与体内ADM代谢相互作用。总之，WYX-5可能是MDR癌症联合化疗研究的有希望的候选者。

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