Current Understanding of Drug Disposition in Kidney Disease
Current Understanding of Drug Disposition in Kidney Disease
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DOI：
10.1177/0091270011413588
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发表时间：
2012-01-01
影响因子：
2.9
通讯作者：
Pichette, Vincent
中科院分区：
文献类型：
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作者：
Naud, Judith;Nolin, Thomas D.;Pichette, Vincent
慢性肾脏疾病(CKD)患者占美国人口的13%。CKD已被证明可以显著改变非肾消除药物的药物处置。事实上，已有报道在肠道和肝脏药物代谢酶以及摄取和外排转运体的表达和功能方面进行了修饰。尿毒症毒素、炎性细胞因子和甲状旁腺激素被认为是病因。这些变化可能对药物处置产生重要的临床影响，如果在肾功能受损的患者中不调整剂量就给予这些变化，可能会导致意外毒性。本文综述了最近的临床前和临床研究，并介绍了CKD对药物吸收、分布、代谢和排泄的影响的研究现状。
Patients with chronic kidney disease (CKD) represent 13% of the American population. CKD has been shown to significantly alter drug disposition of nonrenally eliminated drugs. Indeed, modifications in the expression and function of intestinal and hepatic drug metabolism enzymes and uptake and efflux transporters have been reported. Uremic toxins, inflammatory cytokines, and parathyroid hormone have been implicated as causes. These changes con have an important clinical impact on drug disposition and lead to unintended toxicity if they ore administered without dose adjustment in patients with impaired kidney function. This review summarizes recent preclinical and clinical studies and presents the current understanding of the effect of CKD on drug absorption, distribution, metabolism, and excretion.