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Laropiprant in Combination With Extended‐Release Niacin Does Not Alter Urine 11‐Dehydrothromboxane B 2 , a Marker of In Vivo Platelet Function, in Healthy, Hypercholesterolemic, and Diabetic Subjects
Author(s) -
Lauring Brett,
Dishy Victor,
Luo WenLin,
Laterza Omar,
Patterson Jaclyn,
Cote Josee,
Chao Alice,
Larson Patrick,
Gutierrez Maria,
Wagner John A.,
Lai Eseng
Publication year - 2009
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/0091270009339593
Subject(s) - niacin , pharmacology , in vivo , dyslipidemia , platelet , medicine , chemistry , platelet activation , endocrinology , diabetes mellitus , biology , microbiology and biotechnology
Laropiprant, an antagonist of the PGD 2 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 PGD 2 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 B 2 (11‐dTxB 2 ), 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‐dTxB 2 levels compared to ER niacin alone in healthy, hypercholesterolemic, or diabetic subjects. In hypercholesterolemic and diabetic subjects, laropiprant did not increase urinary 11‐dTxB 2 levels compared to placebo. These results demonstrate that laropiprant does not enhance in vivo platelet reactivity, either alone or in combination with niacin.