Current understanding of drug disposition in kidney disease.
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 can have an important clinical impact on drug disposition and lead to unintended toxicity if they are 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.
Service de néphrologie et Centre de recherche de l’Hôpital Maisonneuve-Rosemont, Faculté de Médecine, Université de Montréal, Québec, Canada.
Judith
J
Naud
Thomas D
TD
Nolin
Francois A
FA
Leblond
Vincent
V
Pichette
D000042:Absorption; D000818:Animals; D006801:Humans; D007668:Kidney / Q000378:metabolism; D007676:Kidney Failure, Chronic / Q000188:drug therapy / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D008657:Metabolic Clearance Rate; D010599:Pharmacokinetics