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Straka_RJ

Research Abstracts Online
January 2009 - March 2010

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University of Minnesota Twin Cities
College of Pharmacy
Department of Experimental and Clinical Pharmacology

PI: Robert J. Straka

The Impact of Genetic Determinants of Fenofibrate's Pharmacokinetics on Lipid Response

The goal of this project is to identify the role of drug-metabolizing genes in determining response to a lipid-lowering drug (fenofibrate). Dyslipidemia is a major risk factor contributing to cardiovascular (CV) disease morbidity and mortality. In spite of optimal low-density lipoprotein lowering with statins, CV risk remains high for patients with elevated triglyceride/low high-density lipoprotein profiles. Because of substantial variability in response to drugs, not all patients benefit equally from lipid-lowering drug therapy. Identifying sources of variability in response to lipid lowering drugs would aid clinicians seeking to optimize drug selection for these patients. One source of variability may include genetic factors affecting drug disposition and thus exposure to drug target receptor(s). Fenofibric acid, the active moiety of fenofibrate, acts on PPAR-alpha receptors to effect changes in lipid fractions through transcription. However, fenofibric acid concentrations, and thus exposure to the PPAR-alpha receptor, are affected by inactivating enzymes known as UDP-glucuronosyltransferases (UGTs). For some drugs genetic variations in UGT activity have been shown to affect drug concentrations and hence response (including toxicity). The central hypothesis of this research is that genetic variations in UGTs modulate fenofibrate’s effect on serum triglycerides and thus influence therapeutic outcomes.

Group Members

Azher Arafah, Graduate Student
Chris Boreen, Undergraduate Student
Brittany Hogan, Undergraduate Student
Preethi Krishnan, Undergraduate Student
Dianna Seng, Undergraduate Student