Department of Pharmacology, Pomeranian Medical University, Powstancow Wlkp 72, 70-111 Szczecin, Poland.
Institute of Pharmacology and Toxicology, Rostock University Medical Center, 18051 Rostock, Germany.
Int J Mol Sci. 2020 Aug 10;21(16):5737. doi: 10.3390/ijms21165737.
Emerging information suggests that liver pathological states may affect the expression and function of membrane transporters in the gastrointestinal tract and the kidney. Altered status of the transporters could affect drug as well as endogenous compounds handling with subsequent clinical consequences. It seems that changes in intestinal and kidney transporter functions provide the compensatory activity of eliminating endogenous compounds (e.g., bile acids) generated and accumulated due to liver dysfunction. A literature search was conducted on the Ovid and PubMed databases to select relevant in vitro, animal and human studies that have reported expression, protein abundance and function of the gastrointestinal and kidney operating ABC (ATP-binding cassette) transporters and SLC (solute carriers) carriers. The accumulated data suggest that liver failure-associated transporter alterations in the gastrointestinal tract and kidney may affect drug pharmacokinetics. The altered status of drug transporters in those organs in liver dysfunction conditions may provide compensatory activity in handling endogenous compounds, affecting local drug actions as well as drug pharmacokinetics.
新出现的信息表明，肝脏病理状态可能会影响胃肠道和肾脏中膜转运体的表达和功能。转运体的改变状态可能会影响药物以及内源性化合物的处理，从而产生随后的临床后果。似乎肠道和肾脏转运体功能的变化为消除由于肝功能障碍而产生和积累的内源性化合物（例如胆汁酸）提供了补偿性的清除活性。在 Ovid 和 PubMed 数据库上进行了文献检索，以选择已报道胃肠道和肾脏 ABC（ATP 结合盒）转运体和 SLC（溶质载体）载体表达、蛋白丰度和功能的相关体外、动物和人体研究。累积数据表明，与肝功能衰竭相关的胃肠道和肾脏转运体改变可能会影响药物的药代动力学。在肝功能障碍情况下，这些器官中药物转运体的改变状态可能会为处理内源性化合物提供补偿性活性，从而影响局部药物作用和药物药代动力学。
