Pfizer Global Research & Development, Department of Pharmacokinetics, Dynamics & Metabolism, 10646 Science Center Drive, San Diego, CA 92121, USA.
Expert Opin Drug Metab Toxicol. 2010 May;6(5):603-19. doi: 10.1517/17425251003610640.
P-glycoprotein (P-gp) is the most characterized drug transporter in terms of its clinical relevance for pharmacokinetic disposition and interaction with other medicines. Clinically significant P-gp related drug interactions appear restricted to digoxin. P-gp may act as a major barrier to current and effective drug treatment in a number of diseases including cancer, AIDS, Alzheimer's and epilepsy due to its expression in tumors, lymphocytes, cell membranes of brain capillaries and the choroid plexus.
This review summarizes the current understanding of P-gp structure/function, clinical importance of P-gp related drug interactions and the modulatory role this transporter may contribute towards drug efficacy in disease states such as cancer, AIDS, Alzheimer's and epilepsy.
The reader will gain an understanding that the clinical relevance of P-gp in drug interactions is limited. In certain disease states, P-gp in barrier tissues can modulate changes in regional distribution.
P-gp inhibition in isolation will not result in clinically important alterations in systemic exposure; however, P-gp transport may be of significance in barrier tissues (tumors, lymphocytes, brain) resulting in attenuated efficacy.
P-糖蛋白（P-gp）是最具特征的药物转运蛋白，就其对药代动力学处置和与其他药物相互作用的临床相关性而言。临床上显著的 P-gp 相关药物相互作用似乎仅限于地高辛。由于 P-gp 在肿瘤、淋巴细胞、脑毛细血管细胞膜和脉络丛中表达，它可能成为许多疾病（包括癌症、艾滋病、阿尔茨海默病和癫痫）当前和有效药物治疗的主要障碍。
这篇综述总结了目前对 P-gp 结构/功能的理解、P-gp 相关药物相互作用的临床重要性以及该转运蛋白在癌症、艾滋病、阿尔茨海默病和癫痫等疾病状态下可能对药物疗效的调节作用。
读者将了解到 P-gp 在药物相互作用中的临床相关性是有限的。在某些疾病状态下，屏障组织中的 P-gp 可以调节区域性分布的变化。
单独的 P-gp 抑制不会导致系统暴露的临床重要改变；然而，P-gp 转运可能在屏障组织（肿瘤、淋巴细胞、脑）中具有重要意义，导致疗效减弱。
