Laropiprant in Combination With Extended-Release Niacin Does Not Alter Urine 11-Dehydrothromboxane B2, a Marker of In Vivo Platelet Function, in Healthy, Hypercholesterolemic, and Diabetic Subjects


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Abstract

Laropiprant, an antagonist of the PGD2 receptor, DP1, is effective in reducing the flushing symptoms associated with extended-release (ER) niacin and thereby improves the tolerability of niacin therapy for dyslipidemia. Because PGD2 has been reported to inhibit platelet aggregation in vitro, it has been speculated that antagonism of DP1 may enhance platelet reactivity. Three clinical studies evaluated the potential effect of laropiprant, with or without coadministration of ER niacin, on in vivo platelet function in healthy subjects and hypercholesterolemic or diabetic subjects by measuring urinary levels of 11-dehydrothromboxane B2 (11-dTxB2), a marker of in vivo platelet activation. Following 7 days of multiple-dose administration, coadministration of laropiprant with ER niacin did not increase urinary 11-dTxB2 levels compared to ER niacin alone in healthy, hypercholesterolemic, or diabetic subjects. In hypercholesterolemic and diabetic subjects, laropiprant did not increase urinary 11-dTxB2 levels compared to placebo. These results demonstrate that laropiprant does not enhance in vivo platelet reactivity, either alone or in combination with niacin.

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