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- Title
Assessment of potential pharmacokinetic interactions of ezetimibe/simvastatin and extended-release niacin tablets in healthy subjects.
- Authors
Kosoglou, Teddy; Zhu, Yali; Statkevich, Paul; Triantafyllou, Ilias; Taggart, William; Xuan, Fengjuan; Kim, Kenneth; Cutler, David
- Abstract
Background: Efforts to lower plasma lipid levels sometimes require multiple agents with different mechanisms of action to achieve results specified by national treatment guidelines. Methods: This was an open-label, randomized, three-period, multiple-dose crossover study that assessed the potential for pharmacokinetic interaction between extended-release niacin and ezetimibe/simvastatin and their major metabolites. Eighteen adults received three randomized treatments: (A) extended-release (ER) niacin 1000 mg/day for 2 days, followed by 2000 mg/day for 5 days; (B) ezetimibe/simvastatin 10 mg/20 mg/day; (C) coadministration of Treatments A and B. Treatments were given once a day after a low fat breakfast for a total of 7 days, with a 7-day inter-dose period. Results: There were small (mean ≤35%) increases in drug exposure for all analytes after coadministration of ER niacin and ezetimibe/simvastatin 10 mg/20 mg. The least-square mean between treatment C (maximum plasma concentration) ratios (×100) were 97, 98, and 109% for ezetimibe, simvastatin and niacin, respectively. The corresponding ratios for total ezetimibe, simvastatin acid, and nicotinuric acid were 99, 118, and 110%. The AUC (area under the plasma concentration-time curve from time zero to 24 h after dosing) ratios for ezetimibe, simvastatin, and niacin were 109, 120, and 122%, respectively, and the corresponding ratios for total ezetimibe, simvastatin acid, and nicotinuric acid were 126, 135 and 119%. Conclusion: There is a small pharmacokinetic drug interaction between ER niacin and ezetimibe/simvastatin and although this is not considered to be clinically significant, the concomitant use of these drugs should be appropriately monitored, especially during the niacin titration period.
- Subjects
ANALYSIS of variance; ANTILIPEMIC agents; BIOAVAILABILITY; COMBINATION drug therapy; CLINICAL trials; CONFIDENCE intervals; CONTROLLED release preparations; CROSSOVER trials; DRUG interactions; HYPERLIPIDEMIA; NIACIN; RESEARCH funding; DRUG dosage
- Publication
European Journal of Clinical Pharmacology, 2011, Vol 67, Issue 5, p483
- ISSN
0031-6970
- Publication type
Article
- DOI
10.1007/s00228-010-0955-6