Pharmacokinetic and pharmacodynamic implications of P-glycoprotein modulation

被引:171
作者
Matheny, CJ [1 ]
Lamb, MW [1 ]
Brouwer, KLR [1 ]
Pollack, GM [1 ]
机构
[1] Univ N Carolina, Sch Pharm, Div Drug Delivery & Disposit, Chapel Hill, NC 27599 USA
来源
PHARMACOTHERAPY | 2001年 / 21卷 / 07期
关键词
D O I
10.1592/phco.21.9.778.34558
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
P-glycoprotein (P-gp) is a cell membrane-associated protein that transports a variety of drug substrates. Although P-gp has been studied extensively as a mediator of multidrug resistance in cancer, only recently has the role of P-gp expressed in normal tissues as a determinant of drug pharmaco kinetics and pharmacodynamics been examined. P-glycoprotein is present in organ systems that influence drug absorption (intestine), distribution to site of action (central nervous system and leukocytes), and elimination (liver and kidney), as well as several other tissues. Many marketed drugs inhibit P-gp function, and several compounds are under development as P-gP inhibitors. Similarly, numerous drugs can induce P-gp expression. While P-gp induction does not have a therapeutic role, P-gp inhibition is an attractive therapeutic approach to reverse multidrug resistance. Clinicians should recognize that P-gp induction or inhibition may have a substantial effect on the pharmacokinetics and pharmaco dynamics of concomitantly administered drugs that are substrates for this transporter.
引用
收藏
页码:778 / 796
页数:19
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