Effects of Laropiprant, a Selective Prostaglandin D2 Receptor 1 Antagonist, on the Steady-State Pharmacokinetics of Digoxin in Healthy Adult Subjects

• Published in: Journal of clinical pharmacology 2010-07, Vol.50 (7), p.823-828
• Main Authors: Liu, Fang, Vessey, Laura, Wenning, Larissa, Connolly, Sandra, Buckland, Melissa, Johnson-Levonas, Amy O., Denker, Andrew, Wagner, John A., Lai, Eseng
• Format: Article
• Language: English
• Subjects: Adult; Aged; Area Under Curve; Cardiotonic Agents - pharmacokinetics; Confidence intervals; Cross-Over Studies; Digoxin; Digoxin - pharmacokinetics; Double-Blind Method; Drug Interactions; Electrocardiography - drug effects; Female; Half-Life; Humans; Indoles - adverse effects; Indoles - pharmacology; laropiprant; Male; pharmacokinetics; Receptors, Immunologic - antagonists & inhibitors; Receptors, Prostaglandin - antagonists & inhibitors; Young Adult
• ISSN: 0091-2700; 1552-4604
• DOI: 10.1177/0091270009356571

Laropiprant, a prostaglandin D2 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 (AUC0‐∞) for immunoreactive digoxin fell within 0.80 to 1.25. The AUC0‐∞ and maximum observed plasma concentration (Cmax) 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 Cmax 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 (∼10%) following coadministration of laropiprant and digoxin is not considered to be clinically meaningful.