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Statin/fibrate combination in patients with metabolic syndrome or diabetes: evaluating the risks of pharmacokinetic drug interactions.
Expert Opin Drug Saf 2006; 5(1):145-56EO

Abstract

Patients with the metabolic syndrome and/or Type 2 diabetes mellitus continue to have a high risk of coronary heart disease (CHD) and progression of atherosclerotic lesions despite aggressive statin therapy. Although the National Cholesterol Education Programme Adult Treatment Panel III guidelines recommend the use of fibrates in combination with statins in patients at very high risk of CHD (e.g., patients at the low-density lipoprotein cholesterol target with high triglycerides and low high-density lipoprotein cholesterol, many physicians remain reluctant to use these combinations due to concerns of myotoxicity. Recently conducted metabolic and pharmacokinetic drug-drug interaction studies using gemfibrozil or fenofibrate in combination with five commonly used statins demonstrated a widely different drug interaction potential for these two fibrates. Gemfibrozil causes a 2- to 6-fold increase in statin area under the curve and increases the exposure to many recently approved drugs for the treatment of diabetes. Alternatively, fenofibrate does not adversely affect either the metabolism or pharmacokinetics of the statins studied. These pharmacokinetic differences appear to translate into less potential for interactions with fenofibrate/statin combination therapy compared to gemfibrozil/statin co-administration. The Action to Control Cardiovascular Risk in Diabetes (ACCORD) study in 10,000 patients with Type 2 diabetes mellitus is testing the efficacy and safety of fenofibrate/statin combination.

Authors+Show Affiliations

Rush University, Preventive Cardiology Center, Rush-Presbyterian-St. Luke's Medical Center, 515 State Street, Suite 2700, Chicago, IL, USA. michaeldavidson@radiantresearch.com

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

16370963

Citation

Davidson, Michael H.. "Statin/fibrate Combination in Patients With Metabolic Syndrome or Diabetes: Evaluating the Risks of Pharmacokinetic Drug Interactions." Expert Opinion On Drug Safety, vol. 5, no. 1, 2006, pp. 145-56.
Davidson MH. Statin/fibrate combination in patients with metabolic syndrome or diabetes: evaluating the risks of pharmacokinetic drug interactions. Expert Opin Drug Saf. 2006;5(1):145-56.
Davidson, M. H. (2006). Statin/fibrate combination in patients with metabolic syndrome or diabetes: evaluating the risks of pharmacokinetic drug interactions. Expert Opinion On Drug Safety, 5(1), pp. 145-56.
Davidson MH. Statin/fibrate Combination in Patients With Metabolic Syndrome or Diabetes: Evaluating the Risks of Pharmacokinetic Drug Interactions. Expert Opin Drug Saf. 2006;5(1):145-56. PubMed PMID: 16370963.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Statin/fibrate combination in patients with metabolic syndrome or diabetes: evaluating the risks of pharmacokinetic drug interactions. A1 - Davidson,Michael H, PY - 2005/12/24/pubmed PY - 2006/3/15/medline PY - 2005/12/24/entrez SP - 145 EP - 56 JF - Expert opinion on drug safety JO - Expert Opin Drug Saf VL - 5 IS - 1 N2 - Patients with the metabolic syndrome and/or Type 2 diabetes mellitus continue to have a high risk of coronary heart disease (CHD) and progression of atherosclerotic lesions despite aggressive statin therapy. Although the National Cholesterol Education Programme Adult Treatment Panel III guidelines recommend the use of fibrates in combination with statins in patients at very high risk of CHD (e.g., patients at the low-density lipoprotein cholesterol target with high triglycerides and low high-density lipoprotein cholesterol, many physicians remain reluctant to use these combinations due to concerns of myotoxicity. Recently conducted metabolic and pharmacokinetic drug-drug interaction studies using gemfibrozil or fenofibrate in combination with five commonly used statins demonstrated a widely different drug interaction potential for these two fibrates. Gemfibrozil causes a 2- to 6-fold increase in statin area under the curve and increases the exposure to many recently approved drugs for the treatment of diabetes. Alternatively, fenofibrate does not adversely affect either the metabolism or pharmacokinetics of the statins studied. These pharmacokinetic differences appear to translate into less potential for interactions with fenofibrate/statin combination therapy compared to gemfibrozil/statin co-administration. The Action to Control Cardiovascular Risk in Diabetes (ACCORD) study in 10,000 patients with Type 2 diabetes mellitus is testing the efficacy and safety of fenofibrate/statin combination. SN - 1744-764X UR - https://www.unboundmedicine.com/medline/citation/16370963/Statin/fibrate_combination_in_patients_with_metabolic_syndrome_or_diabetes:_evaluating_the_risks_of_pharmacokinetic_drug_interactions_ L2 - http://www.tandfonline.com/doi/full/10.1517/14740338.5.1.145 DB - PRIME DP - Unbound Medicine ER -