title: Drug Disposition Issues in CKD: Implications for Drug Discovery and Regulatory Approval.
abstract: Patients with chronic kidney disease (CKD) have several comorbidities that require pharmacologic intervention including hypertension, diabetes, anemia, and cardiovascular disease. Advanced CKD patients (eg, treated with hemodialysis) take an average of 12 medications concurrently and are known to suffer from an increased number of medication-related adverse drug events. Recent basic and clinical research has identified altered renal and nonrenal drug clearance in CKD as one mediator of the increased adverse drug events observed in this patient population. This review will briefly describe pharmacokinetic considerations in CKD, review the Food and Drug Administration guidelines for performing pharmacokinetic studies in CKD patients, and outline the roles of academia, industry, and regulatory agencies in improving drug safety in CKD patients.
authors.affiliation: Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, The University of Western Ontario, London, Ontario, Canada; Division of Nephrology, Department of Medicine, Schulich School of Medicine and Dentistry, The University of Western Ontario; Lawson Health Research Institute, London, Ontario, Canada; and Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, The University of Western Ontario; Division of Nephrology, Department of Medicine, Schulich School of Medicine and Dentistry, The University of Western Ontario; Lawson Health Research Institute, London, Ontario, Canada.
authors.forename: Alvin
authors.initials: A
authors.lastname: Tieu
authors.affiliation: Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, The University of Western Ontario, London, Ontario, Canada; Division of Nephrology, Department of Medicine, Schulich School of Medicine and Dentistry, The University of Western Ontario; Lawson Health Research Institute, London, Ontario, Canada; and Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, The University of Western Ontario; Division of Nephrology, Department of Medicine, Schulich School of Medicine and Dentistry, The University of Western Ontario; Lawson Health Research Institute, London, Ontario, Canada.
authors.forename: Andrew A
authors.initials: AA
authors.lastname: House
authors.affiliation: Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, The University of Western Ontario, London, Ontario, Canada; Division of Nephrology, Department of Medicine, Schulich School of Medicine and Dentistry, The University of Western Ontario; Lawson Health Research Institute, London, Ontario, Canada; and Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, The University of Western Ontario; Division of Nephrology, Department of Medicine, Schulich School of Medicine and Dentistry, The University of Western Ontario; Lawson Health Research Institute, London, Ontario, Canada. Electronic address: Brad.Urquhart@schulich.uwo.ca.
authors.forename: Bradley L
authors.initials: BL
authors.lastname: Urquhart
mesh_terms: D035843:Biomedical Research / Q000592:standards*; D017277:Drug Approval; D055808:Drug Discovery; D004345:Drug Industry; D006077:Government Agencies; D006801:Humans; D010599:Pharmacokinetics; D017410:Practice Guidelines as Topic; D051436:Renal Insufficiency, Chronic / Q000150:complications / Q000378:metabolism* / Q000628:therapy; D012380:Role; D014481:United States; D014486:United States Food and Drug Administration; D014495:Universities
keywords: Adverse events; CKD; Drug disposition; Drug safety; Pharmacokinetics