Suppression Of Niacin Induced Flushing Symptoms With A Dp1 Receptor Antagonist

Niacin is an effective therapy for the treatment of dyslipidemia, but its widespread use is limited by bothersome symptoms of flushing. Several lines of evidence suggest that niacin induced flushing is mediated primarily through prostaglandin D 2 (PGD 2 ). This study investigates the effectiveness of MK-0524, a potent, selective, orally active DP1-receptor antagonist to suppress flushing symptoms associated with an extended release (ER) niacin. This was a double-blind, placebo controlled, 6-period, Phase I crossover study in which cutaneous vasodilation, as assessed by symptoms scores of flushing, and by laser doppler Doppler perfusion imaging (LDPI), was quantified following administration of a single oral dose of MK-0524 (30, 100, or 300 mg), 325 mg of aspirin, or matching placebo and 1500 mg NIASPAN ™ . Concomitant treatment with 300 mg of MK-0524 results in ~78% reduction in peak flushing score. As shown in the figure, of 18 subjects, 12 reported moderate or severe flushing with NIASPAN ™ alone, compared to 2 when treated concurrently with either 100 mg or 300 mg of MK-0524 and 8 when pre-treated with 325 mg aspirin. Increases in skin perfusion following NIASPAN ™ (measured by LDPI) were also reduced by treatment with 100 mg and 300 mg MK-0524. These findings suggest that MK-0524 will improve the tolerability of niacin therapy, and thus may increase the acceptance of niacin therapy in patients with increased cardiovascular risk.