Life Sciences Commons^™

The Role Of Drug Transporters In Statin-Induced Myopathy, Michael J. Knauer

Electronic Thesis and Dissertation Repository

Statins are the first line therapy for treatment and prevention of cardiovascular disease. The 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors, or statins, reduce plasma cholesterol levels by inhibiting the rate-limiting step in cholesterol biosynthesis. While statins are well tolerated, up to 15% of patients develop myopathy, manifesting as muscle aches and pain and in rare cases, potentially life-threatening statin-induced rhabdomyolysis. Given that approximately 3 to 4 million Canadians are treated with statins, an estimated 500,000 patients experience associated skeletal muscle side effects that may prevent the continued treatment of hypercholesterolemia. Despite the prevalence of this side effect, little is known regarding …

Intestinal And Hepatic Drug Transporters And Their Role In The Disposition Of Lipid-Lowering Drugs, Ute I. Schwarz

Electronic Thesis and Dissertation Repository

Membrane transporters are widely recognized for their role in drug disposition in humans. Differences in drug concentration among individuals for drugs used to treat cardiovascular diseases, such as statins and ezetimibe, may result from alteration in hepatic and intestinal transporter function due to genetic, clinical or environmental factors, causing variability in drug efficacy or toxicity.

The closely related uptake transporters organic anion-transporting polypeptides OATP1B3 and OATP1B1, are expressed in human liver sharing numerous drug substrates, including 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors, or statins. Recently, a transport-deficient OATP1B1 variant was associated with increased statin exposure and toxicity, however little is known regarding …