| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Sign In to gain access to subscriptions and/or personal tools.
|
|
|
|||||||
Sign In to gain access to subscriptions and/or personal tools. |
|||||||||
DRUG INTERACTIONS |
From Merck Research Laboratories, West Point, Pennsylvania (Dr Bergman, Dr Zhao, Mr Valesky, Ms Liu, Dr Prueksaritanont, Mr Qiu, Dr Vega); Merck Research Laboratories, Blue Bell, Pennsylvania (Dr Murphy, Ms Burke, Dr Paolini); Merck Research Laboratories, Rahway, New Jersey (Dr He, Dr Hartford); and Clinical Pharmacology Associates, Miami, Florida (Dr Lasseter).
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 (AUC0-24h, Cmax, and tmax) 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 AUC0-24h (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) AUC0-24h and Cmax 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.
Key Words: Fenofibrate • simvastatin • pharmacokinetics • drug-drug interaction • HMG-CoA reductase inhibitor
Address for reprints: Arthur J. Bergman, PhD, Merck Research Laboratories, WP75-100, Sumneytown Pike, West Point, PA 19486.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati 
Twitter What's this?
This article has been cited by other articles:
|
|
 |
|
  M. Miller Dyslipidemia and cardiovascular risk: the importance of early prevention QJM, September 1, 2009; 102(9): 657 - 667. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. B. Richards, G. A. Walker, A. Mandagere, M. H. Magee, and L. S. Henderson Effect of Ketoconazole on the Pharmacokinetic Profile of Ambrisentan J. Clin. Pharmacol., June 1, 2009; 49(6): 719 - 724. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Zhu, W. M. Awni, B. Hosmane, M. T. Kelly, D. J. Sleep, J. C. Stolzenbach, K. Wan, T. O. Chira, and R. S. Pradhan ABT-335, the Choline Salt of Fenofibric Acid, Does Not Have a Clinically Significant Pharmacokinetic Interaction With Rosuvastatin in Humans J. Clin. Pharmacol., January 1, 2009; 49(1): 63 - 71. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. R. White Jr Do People With Diabetes Need Statins? The Diabetes Educator, July 1, 2008; 34(4): 664 - 673. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Zambon and K. Cusi The role of fenofibrate in clinical practice Diabetes and Vascular Disease Research, September 1, 2007; 4(3_suppl): S15 - S20. [Abstract] [PDF]
|
|
|
|
 |
|
 T. C. Goosen, J. N. Bauman, J. A. Davis, C. Yu, S. I. Hurst, J. A. Williams, and C.-M. Loi Atorvastatin Glucuronidation Is Minimally and Nonselectively Inhibited by the Fibrates Gemfibrozil, Fenofibrate, and Fenofibric Acid Drug Metab. Dispos., August 1, 2007; 35(8): 1315 - 1324. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Devaraj, E. Chan, and I. Jialal Direct Demonstration of an Antiinflammatory Effect of Simvastatin in Subjects with the Metabolic Syndrome J. Clin. Endocrinol. Metab., November 1, 2006; 91(11): 4489 - 4496. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. N. Ginsberg REVIEW: Efficacy and Mechanisms of Action of Statins in the Treatment of Diabetic Dyslipidemia J. Clin. Endocrinol. Metab., February 1, 2006; 91(2): 383 - 392. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Yufu, K. Hirano, D. Bi, M. Hirano, J. Nishimura, Y. Iwamoto, and H. Kanaide Rac1 Regulation of Surface Expression of Protease-Activated Receptor-1 and Responsiveness to Thrombin in Vascular Smooth Muscle Cells Arterioscler Thromb Vasc Biol, July 1, 2005; 25(7): 1506 - 1511. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. M. Grundy Atherosclerosis Imaging and the Future of Lipid Management Circulation, December 7, 2004; 110(23): 3509 - 3511. [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
