Mechanisms of P-Glycoprotein Alteration During Anticancer Treatment: Role in the Pharmacokinetic and Pharmacological Effects of Various Substrate Drugs

Journal of Pharmacological Sciences

Kazuo Nakamoto¹  Shogo Tokuyama¹  Takuro Kobori¹  Shinichi Harada¹ 

[1] Department of Clinical Pharmacy, School of Pharmaceutical Sciences, Kobe Gakuin University, Japan

关键词: P-glycoprotein;    anticancer drug;    drug-drug interaction;    opioid;    cancer;   

DOI  :  10.1254/jphs.14R01CR

学科分类：药学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(125)Cited-By(3)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.

【 授权许可】

Unknown