Clinical and Pharmacogenomic Predictors of Statin Disposition and Response

Wednesday, February 19, 2014
10:00 a.m.-11:00 a.m.
FDA WO Campus, Bldg. 2 room 2031
Ann Anonsen
aannsen@umd.edu

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Richard B. Kim, MD, FRCPC, FACP-Wolfe Medical Research Chair in Pharmacogenomics, Professor & Chair, Division of Clinical Pharmacology, Director, Center for Clinical & Therapeutics Department of Medicine, University of Western Ontario, Canada

Abstract:

Statin class of lipid lowering medications are widely prescribed. Although their use is associated with overall improvement in cardiovascular outcomes, adverse events particularly in relation to muscle pain and weakness are common side effects of statin use, which in rare cases can lead to a rare but life-threatening form of muscle damage known as rhabdomyolysis. In 2001, our group was the first describe commonly occurring genetic variation in a liver-specific drug uptake transporter known as OATP1B1 (previously known as OATP-C and OATP2), encoded by the SLCO1B1 gene. In 2008, a genome wide association study (GWAS) linked a commonly occurring loss of function genetic variation in SLCO1B1 that our group had noted in 2001, as the most robust predictor of simvastatin-associated myopathy. In this presentation, current available information with regards to pharmacogenetic predictors of statin myopathy and adverse events will be outlined. In addition, our recently published study of atorvastatin and rosuvastatin concentration in 299 patients in a clinical setting that showed statin concentrations vary by ≈45-fold among patients taking the same dose will also be presented. In addition, we observed that ≈50% of patients taking the highest statin doses are predicted to have statin concentrations higher than the 90th percentile. We propose a individualized statin dosing algorithm that incorporates clinical as well as pharmacogenomic variables for reducing the risk of statin myopathy.

Bio:

Dr. Kim received his medical degree from the University of Saskatchewan in 1987. After completing an internship and residency training in Internal Medicine, he went on to carry out fellowship training in Clinical Pharmacology at Vanderbilt University from 1991-1994, and then remained at Vanderbilt as a faculty member in Clinical Pharmacology where he rose to the rank to tenured full Professor by 2004. Since 2006, he has been Professor and Chair of the Division of Clinical Pharmacology, and holds the Wolfe Medical Research Chair in Pharmacogenomics at Western. Areas of active research include in vitro and in vivo models of drug transporters, pharmacogenetics of drug metabolizing enzymes and transporters, as well as patient oriented clinical research.  The goal is that of better understanding the molecular basis of interindividual differences in drug disposition and the application of such finding to the emerging field of Personalized Medicine. He is an elected Member of the American Society for Clinical Investigation (ASCI) and Fellow of the American Association of Pharmaceutical Scientists (AAPS) and Canadian Academy of Health Sciences (CAHS).

 

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