Drug Disposition Issues in CKD: Implications for Drug Discovery and Regulatory Approval

Alvin Tieu; Andrew A House; Bradley L Urquhart

doi:10.1053/j.ackd.2016.01.013

Drug Disposition Issues in CKD: Implications for Drug Discovery and Regulatory Approval

Adv Chronic Kidney Dis. 2016 Mar;23(2):63-6. doi: 10.1053/j.ackd.2016.01.013.

Authors

Alvin Tieu¹, Andrew A House¹, Bradley L Urquhart²

Affiliations

¹ 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.
² 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.

PMID: 26979144
DOI: 10.1053/j.ackd.2016.01.013

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.

Keywords: Adverse events; CKD; Drug disposition; Drug safety; Pharmacokinetics.

Publication types

Review

MeSH terms

Biomedical Research / standards*
Drug Approval
Drug Discovery
Drug Industry*
Government Agencies*
Humans
Pharmacokinetics*
Practice Guidelines as Topic
Renal Insufficiency, Chronic / complications
Renal Insufficiency, Chronic / metabolism*
Renal Insufficiency, Chronic / therapy
Role
United States
United States Food and Drug Administration
Universities*