慢性肾衰竭对药物代谢和转运的影响。
The effect of chronic renal failure on drug metabolism and transport.
作者信息
Dreisbach Albert W, Lertora Juan J L
机构信息
University of Mississippi Medical Center, Division of Nephrology, Department of Medicine, 2500 North State Street, Jackson, MS 39216, USA.
出版信息
Expert Opin Drug Metab Toxicol. 2008 Aug;4(8):1065-74. doi: 10.1517/17425255.4.8.1065.
BACKGROUND
Chronic renal failure (CRF) has been shown to significantly reduce the nonrenal clearance and alter bioavailability of drugs predominantly metabolized by the liver and intestine.
OBJECTIVES
The purpose of this article is to review all significant animal and clinical studies dealing with the effect of CRF on drug metabolism and transport.
METHODS
A search of the National Library of Medicine PubMed was done with terms such as chronic renal failure, cytochrome P450 [CYP], liver metabolism, efflux drug transport and uptake transport, including relevant articles back to 1969.
RESULTS
Animal studies in CRF have shown a significant downregulation (40-85%) of hepatic and intestinal CYP metabolism. High levels of parathyroid hormone, cytokines and uremic toxins have been shown to reduce CYP activity. Phase II reactions and drug transporters such as P-glycoprotein and organic anion transporting polypeptide are also affected.
CONCLUSION
CRF alters intestinal, renal and hepatic drug metabolism and transport producing a clinically significant impact on drug disposition and increasing the risk for adverse drug reactions.
背景
慢性肾衰竭（CRF）已被证明会显著降低非肾清除率，并改变主要经肝脏和肠道代谢的药物的生物利用度。
目的
本文旨在综述所有关于CRF对药物代谢和转运影响的重要动物和临床研究。
方法
使用慢性肾衰竭、细胞色素P450 [CYP]、肝脏代谢、外排药物转运和摄取转运等术语在国立医学图书馆的PubMed数据库中进行检索，包括可追溯至1969年的相关文章。
结果
CRF的动物研究表明，肝脏和肠道CYP代谢显著下调（40 - 85%）。高水平的甲状旁腺激素、细胞因子和尿毒症毒素已被证明会降低CYP活性。II相反应以及药物转运体如P-糖蛋白和有机阴离子转运多肽也受到影响。
结论
CRF改变肠道、肾脏和肝脏的药物代谢及转运，对药物处置产生临床显著影响，并增加药物不良反应的风险。
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