Kunta Jeevan R, Sinko Patrick J
Preclinical Development DMPK, GlaxoSmithkline, King of Prussia, PA 19406, USA.
Curr Drug Metab. 2004 Feb;5(1):109-24. doi: 10.2174/1389200043489144.
The oral route of drug administration remains the most popular and convenient route of administration, despite its many shortcomings and challenges. Although the advantages associated with this route far outweigh any limitations, a prominent limitation relates to the interactions of drugs with intestinal membrane transporters. The complexities of these interactions and their impact on drug absorption and absorption variability are only now becoming recognized. The rapidly growing awareness of transporter-mediated secretion, saturable absorption, and even the concerted actions of transporters in intestinal drug absorption and secretion has attracted the attention of pharmaceutical scientists in academia, the pharmaceutical industry and the regulatory agencies. This is evidenced by the recent rapid accumulation of data in the literature, the routine conducting of transport studies in the discovery and development of drugs, and finally by the recognition of the importance of transporter (e.g. P-glycoprotein and OATP) mediated secretion of drugs by regulatory authorities such as the U.S. Food and Drug Administration. In this mini-review, we focus on the handful of absorptive and secretory transporters that have been relatively well studied and illustrate the impact of these intestinal transporters on oral drug absorption using published reports from preclinical and clinical studies.
尽管口服给药途径存在诸多缺点和挑战，但它仍然是最受欢迎和最方便的给药途径。虽然与该途径相关的优点远远超过任何限制，但一个突出的限制与药物与肠膜转运蛋白的相互作用有关。这些相互作用的复杂性及其对药物吸收和吸收变异性的影响直到现在才被认识到。转运蛋白介导的分泌、饱和吸收，甚至转运蛋白在肠道药物吸收和分泌中的协同作用，这种迅速增长的认识已经引起了学术界、制药行业和监管机构的药物科学家的关注。文献中近期数据的迅速积累、药物研发过程中转运研究的常规开展，以及美国食品药品监督管理局等监管机构对转运蛋白（如P-糖蛋白和有机阴离子转运多肽）介导的药物分泌重要性的认可，都证明了这一点。在本综述中，我们重点关注了少数已得到相对充分研究的吸收性和分泌性转运蛋白，并利用临床前和临床研究的已发表报告来说明这些肠道转运蛋白对口服药物吸收的影响。
