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首页> 外文期刊>Journal of pharmacological sciences. >Mechanisms of P-glycoprotein alteration during anticancer treatment: Role in the pharmacokinetic and pharmacological effects of various substrate drugs
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Mechanisms of P-glycoprotein alteration during anticancer treatment: Role in the pharmacokinetic and pharmacological effects of various substrate drugs

机译：抗癌治疗期间P糖蛋白改变的机制：在各种底物药物的药代动力学和药理作用中的作用

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摘要

In clinical pharmacotherapy, therapeutic benefits and adverse effects of medicines differ substantially between individuals and are often determined by their blood levels. Critical regulators influencing the pharmacokinetics and pharmacodynamics of drugs include drug transporters and drug-metabolizing enzymes. Among these, we have focused on P-glycoprotein (P-gp), a drug efflux transporter. A growing body of evidence indicates that the expression and functional activity of P-gp are altered under several pathological conditions, by exposure to substrate drugs of P-gp, and by ingestion of certain foods. In this critical review, we discuss the mechanisms by which anticancer drugs, most of which are P-gp substrates, alter the expression and functional activity of P-gp in tumors and normal tissues after chronic treatment. Accumulating evidence shows that various transcription factors, in addition to epigenetic and post-translational factors, modulate P-gp expression, which alters the pharmacokinetics and pharmacological effects of drugs. Therefore, it is important to consider individual patients with regard to drug-taking history, as well as levels of P-gp expression and function, when providing clinical pharmacotherapy.
机译：在临床药物治疗中，药物的治疗益处和不良反应在个体之间存在很大差异，并且通常取决于他们的血液水平。影响药物的药代动力学和药效学的关键调节剂包括药物转运蛋白和药物代谢酶。其中，我们专注于药物外排转运蛋白P-糖蛋白（P-gp）。越来越多的证据表明，通过暴露于P-gp的底物药物和摄入某些食物，P-gp的表达和功能活性在几种病理条件下会发生变化。在这篇重要的综述中，我们讨论了抗癌药物（大多数是P-gp底物）通过这些机制改变慢性治疗后肿瘤和正常组织中P-gp的表达和功能活性的机制。越来越多的证据表明，除了表观遗传因素和翻译后因素之外，各种转录因子还调节P-gp表达，从而改变了药物的药代动力学和药理作用。因此，在提供临床药物治疗时，重要的是要考虑各个患者的用药史以及P-gp表达和功能水平。

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