Assessment of potential pharmacokinetic interactions of ezetimibe/simvastatin and extended-release niacin tablets in healthy subjects.
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(max) (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((0-24)) (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%.


CONCLUSIONS
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.
Merck & Co., Inc., Whitehouse Station, NJ, USA. teddy.kosoglou2@merck.com
Teddy
T
Kosoglou
Yali
Y
Zhu
Paul
P
Statkevich
Ilias
I
Triantafyllou
William
W
Taggart
Fengjuan
F
Xuan
Kenneth T
KT
Kim
David L
DL
Cutler
D000328:Adult; D000924:Anticholesteremic Agents / Q000009:adverse effects / Q000493:pharmacokinetics; D001384:Azetidines / Q000009:adverse effects / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D000069438:Ezetimibe; D005260:Female; D006801:Humans; D000960:Hypolipidemic Agents / Q000009:adverse effects / Q000493:pharmacokinetics; D008055:Lipids / Q000097:blood; D008297:Male; D009525:Niacin / Q000009:adverse effects / Q000493:pharmacokinetics*; D009539:Nicotinic Acids / Q000493:pharmacokinetics; D019821:Simvastatin / Q000009:adverse effects / Q000031:analogs & derivatives / Q000493:pharmacokinetics*; D013607:Tablets / Q000009:adverse effects / Q000493:pharmacokinetics
D000924:Anticholesteremic Agents; D001384:Azetidines; D003692:Delayed-Action Preparations; D000960:Hypolipidemic Agents; D008055:Lipids; D009539:Nicotinic Acids; D013607:Tablets; D009525:Niacin; C002477:nicotinuric acid; C063287:simvastatin acid; D019821:Simvastatin; D000069438:Ezetimibe