Krishna R, Mayer L D
Department of Advanced Therapeutics, British Columbia Cancer Agency, BC V5Z 4E6, Vancouver, Canada.
Eur J Pharm Sci. 2000 Oct;11(4):265-83. doi: 10.1016/s0928-0987(00)00114-7.
In recent years, there has been an increased understanding of P-glycoprotein (P-GP)-mediated pharmacokinetic interactions. In addition, its role in modifying the bioavailability of orally administered drugs via induction or inhibition has been also been demonstrated in various studies. This overview presents a background on some of the commonly documented mechanisms of multidrug resistance (MDR), reversal using modulators of MDR, followed by a discussion on the functional aspects of P-GP in the context of the pharmacokinetic interactions when multiple agents are coadministered. While adverse pharmacokinetic interactions have been documented with first and second generation MDR modulators, certain newer agents of the third generation class of compounds have been less susceptible in eliciting pharmacokinetic interactions. Although the review focuses on P-GP and the pharmacology of MDR reversal using MDR modulators, relevance of these drug transport proteins in the context of pharmacokinetic implications (drug absorption, distribution, clearance, and interactions) will also be discussed.
近年来，人们对P-糖蛋白（P-GP）介导的药代动力学相互作用有了更深入的了解。此外，在各种研究中也证实了其通过诱导或抑制作用改变口服药物生物利用度的作用。本综述介绍了一些常见的多药耐药（MDR）机制的背景知识，以及使用MDR调节剂进行逆转的情况，随后讨论了在联合使用多种药物时，P-GP在药代动力学相互作用背景下的功能方面。虽然第一代和第二代MDR调节剂已被证明存在不良药代动力学相互作用，但某些第三代新型化合物在引发药代动力学相互作用方面的敏感性较低。尽管本综述重点关注P-GP以及使用MDR调节剂逆转MDR的药理学，但也将讨论这些药物转运蛋白在药代动力学影响（药物吸收、分布、清除和相互作用）方面的相关性。
