Effects of Extended-Release Niacin and Extended-Release Niacin/Laropiprant on the Pharmacokinetics of Simvastatin in Healthy Subjects.
The use of multiple lipid-modifying agents with different mechanisms of action is often required to regulate lipid levels in patients with dyslipidemia. During combination therapy, alterations in the pharmacokinetics of any of the drugs used and their metabolites may occur. Three separate open-label, randomized, crossover studies evaluated the potential for pharmacokinetic interaction between extended-release niacin (with and without concomitant laropiprant) and simvastatin in healthy subjects. Study 1 used single doses of extended-release niacin and simvastatin; study 2 used multiple-dose coadministration of extended-release niacin/laropiprant and simvastatin in healthy subjects; and study 3 used single doses of both extended-release niacin and the coadministration of extended-release niacin/laropiprant and simvastatin in healthy Chinese subjects. During each treatment period, plasma samples were collected predose and at prespecified postdose time points for pharmacokinetic analyses. The safety and tolerability of simvastatin with and without coadministered extended-release niacin (or extended-release niacin/laropiprant) were assessed by clinical evaluation of adverse experiences. In 2 studies in healthy subjects, modest increases in exposure to simvastatin acid (by ∼60%) by extended-release niacin and extended-release niacin/laropiprant were observed. Based on the clinical experience with simvastatin, these effects are not believed to be clinically meaningful. In the third study on healthy Chinese subjects, no statistically meaningful increases in exposure to simvastatin by extended-release niacin and extended-release niacin/laropiprant were observed. In all populations examined in these studies, the coadministration of extended-release niacin and simvastatin was generally well tolerated.
1Merck & Co., Inc., Whitehouse Station, NJ; 2MSD International GmbH (Singapore Branch); and 3Department of Applied and Computational Mathematics and Statistics, University of Notre Dame, Notre Dame, IN.
Brett
B
Lauring
Victor
V
Dishy
Pieter-Jan
PJ
De Kam
Tami
T
Crumley
Larissa
L
Wenning
Fang
F
Liu
Christine
C
Sisk
John
J
Wagner
Eseng
E
Lai
D000328:Adult; D000368:Aged; D019540:Area Under Curve; D002681:China; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D050171:Dyslipidemias / Q000188:drug therapy*; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D000960:Hypolipidemic Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D007211:Indoles / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D009525:Niacin / Q000008:administration & dosage / Q000494:pharmacology*; D019821:Simvastatin / Q000009:adverse effects / Q000493:pharmacokinetics*
D003692:Delayed-Action Preparations; D000960:Hypolipidemic Agents; D007211:Indoles; C518174:MK-0524; D009525:Niacin; D019821:Simvastatin