PDF(Pubmed)
Abstract：
A large percentage (~60%) of prescription drugs and new molecular entities are designed for oral delivery, which requires passage through a semi-impervious membrane bilayer in the gastrointestinal wall. Passage through this bilayer can be dependent on membrane transporters that regulate the absorption of nutrients or endogenous substrates. Several investigations have provided links between nutrient, endogenous substrate, or drug absorption and the activity of certain membrane transporters. This knowledge has been key in the development of new therapeutics that can alleviate various symptoms of select diseases, such as cholestasis and diabetes. Despite this progress, recent studies revealed potential clinical dangers of unintended altered nutrient or endogenous substrate disposition due to the drug-mediated disruption of intestinal transport activity. This review outlines reports of glucose, folate, thiamine, lactate, and bile acid (re)absorption changes and consequent adverse events as examples. Finally, the need to comprehensively expand research on intestinal transporter-mediated drug interactions to avoid the unwanted disruption of homeostasis and diminish therapeutic adverse events is highlighted.
摘要：
很大比例（约60％）的处方药和新的分子实体被设计用于口服给药，这需要通过胃肠壁中的半不透水膜双层。通过该双层可以依赖于调节营养素或内源性底物吸收的膜转运蛋白。几项调查提供了营养素之间的联系，内源性底物，或药物吸收和某些膜转运蛋白的活性。这些知识一直是开发可以缓解某些疾病的各种症状的新疗法的关键，如胆汁淤积和糖尿病。尽管取得了这些进展,最近的研究表明，由于药物介导的肠道运输活动破坏，导致营养或内源性底物配置意外改变的潜在临床危险。这篇综述概述了葡萄糖的报道，叶酸,硫胺素,乳酸，和胆汁酸（再）吸收变化和随之而来的不良事件为例。最后,需要全面扩大肠道转运蛋白介导的药物相互作用的研究,以避免体内稳态的不必要破坏和减少治疗不良事件.
