1. ¹Department of Clinical Pharmacology, Merck Research Laboratories, Rahway, New Jersey, USA
2. ²Department of Clinical Pharmacology, Merck Research Laboratories, Brussels, Belgium
3. ³Department of Clinical Biostatistics and Decision Sciences, Merck Research Laboratories, Rahway, New Jersey, USA
4. ⁴Department of Clinical Drug Metabolism, Merck Research Laboratories, West Point, Pennsylvania, USA
5. ⁵Algemeen Ziekenhuis Stuivenberg, SGS Biopharma, Antwerp, Belgium
6. ⁶Department of Biochemistry, Merck Frosst Canada, Montreal, Quebec, Canada

Correspondence: E Lai, (eseng_lai@merck.com)

Received 2 November 2006; Accepted 23 January 2007; Published online 28 March 2007.

Abstract

Niacin (nicotinic acid) reduces cardiovascular events in patients with dyslipidemia. However, symptoms associated with niacin-induced vasodilation (e.g., flushing) have limited its use. Laropiprant is a selective antagonist of the prostaglandin D₂ receptor subtype 1 (DP1), which may mediate niacin-induced vasodilation. The aim of this proof-of-concept study was to evaluate the effects of laropiprant (vs placebo) on niacin-induced cutaneous vasodilation. Coadministration of laropiprant 30, 100, and 300 mg with extended-release (ER) niacin significantly lowered flushing symptom scores (by approximately 50% or more) and also significantly reduced malar skin blood flow measured by laser Doppler perfusion imaging. Laropiprant was effective after multiple doses in reducing symptoms of flushing and attenuating the increased malar skin blood flow induced by ER niacin. In conclusion, the DP1 receptor antagonist laropiprant was effective in suppressing both subjective and objective manifestations of niacin-induced vasodilation.