Simvastatin does not have a clinically significant pharmacokinetic interaction with fenofibrate in humans.

Abstract

Simvastatin and fenofibrate are both commonly used lipid-regulating agents with distinct mechanisms of action, and their coadministration may be an attractive treatment for some patients with dyslipidemia. A 2-period, randomized, open-label, crossover study was conducted in 12 subjects to determine if fenofibrate and simvastatin are subject to a clinically relevant pharmacokinetic interaction at steady state. In treatment A, subjects received an 80-mg simvastatin tablet in the morning for 7 days. In treatment B, subjects received a 160-mg micronized fenofibrate capsule in the morning for 7 days, followed by a 160-mg micronized fenofibrate capsule dosed together with an 80-mg simvastatin tablet on days 8 to 14. Because food increases the bioavailability of fenofibrate, each dose was administered with food to maximize the exposure of fenofibric acid. The steady-state pharmacokinetics (AUC(0-24h), C(max), and t(max)) of active and total HMG-CoA reductase inhibitors, simvastatin acid, and simvastatin were determined following simvastatin administration with and without fenofibrate. Also, fenofibric acid steady-state pharmacokinetics were evaluated with and without simvastatin. The geometric mean ratios (GMRs) for AUC(0-24h) (80 mg simvastatin [SV] + 160 mg fenofibrate)/(80 mg simvastatin alone) and 90% confidence intervals (CIs) were 0.88 (0.80, 0.95) and 0.92 (0.82, 1.03) for active and total HMG-CoA reductase inhibitors. The GMRs and 90% CIs for fenofibric acid (80 mg SV + 160 mg fenofibrate/160 mg fenofibrate alone) AUC(0-24h) and C(max) were 0.95 (0.88, 1.04) and 0.89 (0.77, 1.02), respectively. Because both the active inhibitor and fenofibric acid AUC GMR 90% confidence intervals fell within the prespecified bounds of (0.70, 1.43), no clinically significant pharmacokinetic drug interaction between fenofibrate and simvastatin was concluded in humans. The coadministration of simvastatin and fenofibrate in this study was well tolerated.

• Authors: Arthur J Bergman, Gail Murphy, Joanne Burke, Jamie J Zhao, Robert Valesky, Lida Liu, Kenneth C Lasseter, Weili He, Thomayant Prueksaritanont, Yue Qiu, Alan Hartford, Jose M Vega, John F Paolini
• Journal: Journal of clinical pharmacology (J Clin Pharmacol) Vol. 44 Issue 9 Pg. 1054-62 (Sep 2004) ISSN: 0091-2700 [Print] England
• PMID: 15317833 (Publication Type: Clinical Trial, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Hydroxymethylglutaryl-CoA Reductase Inhibitors
• Hypolipidemic Agents
• Simvastatin
• Hydroxymethylglutaryl CoA Reductases
• Fenofibrate

Topics

• Adolescent
• Adult
• Area Under Curve
• Biotransformation
• Blood Cell Count
• Cross-Over Studies
• Drug Interactions
• Electrocardiography (drug effects)
• Female
• Fenofibrate (adverse effects, pharmacokinetics)
• Half-Life
• Humans
• Hydroxymethylglutaryl CoA Reductases (blood)
• Hydroxymethylglutaryl-CoA Reductase Inhibitors (adverse effects, pharmacokinetics)
• Hypolipidemic Agents (adverse effects, pharmacokinetics)
• In Vitro Techniques
• Male
• Microsomes, Liver (metabolism)
• Middle Aged
• Simvastatin (adverse effects, pharmacokinetics)