Effects of laropiprant, a selective prostaglandin D2 receptor 1 antagonist, on the steady-state pharmacokinetics of digoxin in healthy adult subjects.
Laropiprant, a prostaglandin D(2) receptor-1 antagonist shown to reduce flushing symptoms, has been combined with niacin for treatment of dyslipidemia. This open-label, randomized, 2-period crossover study assessed the effects of laropiprant on the pharmacokinetics of digoxin, with 13 healthy subjects randomized to 2 treatments administered in random order with a 10-day or longer washout period: (A) single-dose digoxin 0.5 mg on day 1 and once-daily oral doses of laropiprant 40 mg for 10 days beginning 5 days prior to digoxin dosing (day -5 to day 5); (B) single-dose digoxin 0.5 mg on day 1. Blood was collected over the course of 120 hours post digoxin dose to assess pharmacokinetics of immunoreactive digoxin. Comparability was declared if the 90% confidence interval for the geometric mean ratio of laropiprant+digoxin to digoxin alone of the area under the plasma concentration-time curve from time 0 to infinity (AUC(0-infinity)) for immunoreactive digoxin fell within 0.80 to 1.25. The AUC(0-infinity) and maximum observed plasma concentration (C(max)) geometric mean ratios of immunoreactive digoxin were 0.91 (90% confidence interval, 0.76-1.10) and 1.04 (90% confidence interval, 0.91-1.21), respectively. Median time of occurrence of C(max) and mean half-life of immunoreactive digoxin were comparable in the presence and absence of laropiprant. Coadministration of digoxin and laropiprant was generally well tolerated. The small decrease in exposure to immunoreactive digoxin (approximately 10%) following coadministration of laropiprant and digoxin is not considered to be clinically meaningful.
Liu
Fang
F
Merck Research Laboratories, 126 East Lincoln Ave, P.O. Box 2000, Rahway, NJ 07065-0900, USA.
Vessey
Laura
L
Wenning
Larissa
L
Connolly
Sandra
S
Buckland
Melissa
M
Johnson-Levonas
Amy O
AO
Denker
Andrew
A
Wagner
John A
JA
Lai
Eseng
E
D000328:Adult; D000368:Aged; D019540:Area Under Curve; D002316:Cardiotonic Agents / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D004077:Digoxin / Q000493:pharmacokinetics*; D004311:Double-Blind Method; D004347:Drug Interactions; D004562:Electrocardiography / Q000187:drug effects; D005260:Female; D006207:Half-Life; D006801:Humans; D007211:Indoles / Q000009:adverse effects / Q000494:pharmacology*; D008297:Male; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors*; D011982:Receptors, Prostaglandin / Q000037:antagonists & inhibitors*; D055815:Young Adult
D002316:Cardiotonic Agents; D007211:Indoles; C518174:MK-0524; D011971:Receptors, Immunologic; D011982:Receptors, Prostaglandin; D004077:Digoxin; C036293:prostaglandin D2 receptor