Pharmacokinetic Studies in Patients with Impaired Renal Function
Wednesday, June 18, 2014
10:00 a.m.-11:00 a.m.
FDA-White Oak Bldg. 2, Room 2047E
Arthur J. Atkinson, Jr., M.D., M.A.C.P
Adjunct Professor, Department of Pharmacology, Feinberg School of Medicine
The clinical application of pharmacokinetic principles has facilitated a priori estimates of appropriate drug doses for individual patients. This application of pharmacokinetics perhaps has had its greatest impact on estimating drug dosage for patients with impaired renal function. Because there is a paucity of data to indicate the level of renal impairment at which drug dosage should be reduced, the FDA's Renal Impairment Working Group has drafted Guidance to facilitate the conduct of studies to provide this information. Adding to the complexity of this situation is a controversy regarding whether drug dose adjustments should be based on estimates of glomerular filtration using the statistically-based Modification of Diet in Renal Disease (MDRD) equation or on the Cockcroft and Gault equation that has traditionally been used to estimate creatinine clearance. This presentation will review these issues and will provide best practice suggestions for conducting pharmacokinetic studies in patients with impaired renal function. A case report will also be used to emphasize the importance of using regression methods to characterize the functional relationship between impaired renal function and drug exposure.
Dr. Atkinson received his A.B. degree in Chemistry from Harvard College in 1959 and his M.D. from Cornell University Medical College in 1963. Following medical internship and residency at the Massachusetts General Hospital, he was a Clinical Associate in the Laboratory of Clinical Investigation of the National Institute of Allergy and Infectious Diseases at NIH. He subsequently received postdoctoral training in clinical pharmacology at the University of Cincinnati and was a Visiting Scientist in the Department of Toxicology at the Karolinska Institute before moving to Northwestern University Medical School in 1970 to start the program in clinical pharmacology. While at Northwestern, he and his colleagues set up the first U.S. hospital laboratory devoted to general therapeutic drug monitoring, and worked with what was then the Finnegan Corporation to first implement selected ion monitoring on quadrupole mass spectrometers. They designed and conducted the first clinical investigations to develop the acetylated metabolite of procainamide as a new antiarrhythmic drug, carried out the first pharmacokinetic studies with stable isotope-labeled drugs, and completed basic research that elucidated the physiologic basis of some multicompartmental models of drug distribution. In 1994, Dr. Atkinson was appointed Corporate Vice President for Clinical Development and Medical Affairs at the Upjohn Company. Following the Upjohn-Pharmacia merger, he joined the Center for Drug Development Science at Georgetown University as an Adjunct Professor of Pharmacology. From 1975 to 1979, Dr. Atkinson served as a member of the Pharmacology/Toxicology Program Committee of the National Institute of General Medical Sciences (NIGMS), and from 1984 to 1986, chaired the Pharmacological Sciences Program Committee for that institute. In 1997, he returned to NIH as a Special Expert Consultant in Clinical Pharmacology for NIGMS. The following year, he was appointed Senior Advisor in Clinical Pharmacology to the Director of the NIH Clinical Center where until October 2005 he directed the ClinPRAT postdoctoral training program and initiated the ongoing Clinical Center course on Principles of Clinical Pharmacology. Dr. Atkinson is a Master of the American College of Physicians, and has been President of the Chicago Society of Internal Medicine, President of the American Board of Clinical Pharmacology, and President of the American Society for Clinical Pharmacology and Therapeutics. He currently is an Adjunct Professor in the Department of Pharmacology at the Feinberg School of Medicine, Northwestern University and serves as an Associate Editor of Clinical Pharmacology and Therapeutics. He served as lead editor and major contributing author for all three editions of the text, Principles of Clinical Pharmacology, that is based on the NIH course and was most recently published in 2012 by Academic Press.