Open AccessEffects of Laropiprant, a Selective Prostaglandin D 2 Receptor 1 Antagonist, on the Pharmacokinetics of Rosiglitazone
Author(s) -
Schwartz Jules I.,
Stroh Mark,
Gao Bing,
Liu Fang,
Rosko Kimberly,
Zajic Stefan,
Meehan Alan J.,
Ruckle Jon,
Lai Eseng,
Wagner John A.
Publication year - 2009
Publication title -
cardiovascular therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.818
H-Index - 46
eISSN - 1755-5922
pISSN - 1755-5914
DOI - 10.1111/j.1755-5922.2009.00104.x
Subject(s) - rosiglitazone , medicine , pharmacokinetics , pharmacology , niacin , crossover study , dyslipidemia , endocrinology , diabetes mellitus , receptor , placebo , alternative medicine , pathology
Laropiprant (LRPT), a prostaglandin D 2 receptor‐1 antagonist shown to reduce niacin‐induced flushing symptoms, has been combined with niacin for treatment of dyslipidemia. This open‐label, randomized, 2‐period crossover study assessed the pharmacokinetics of single‐dose rosiglitazone in the presence and absence of multiple‐dose LRPT. Twelve healthy male and female subjects, 34–64 years of age, received two, once‐daily oral treatments in random sequence separated by ≥3‐day washout: (1) multiple‐dose LRPT 40 mg/day for 7 days (Days 1 to 7) coadministered with single‐dose rosiglitazone 4 mg on Day 6; (2) single‐dose rosiglitazone 4 mg on Day 1. Comparability was declared because the 90% confidence interval (CI) for the AUC 0‐∞ geometric mean ratio (GMR; rosiglitazone + LRPT/rosiglitazone alone) [0.92 (0.86, 0.99)], was contained within prespecified bounds (0.70, 1.43). The C max GMR (90% CI) for rosiglitazone was 0.98 (0.95, 1.02). There was no evidence of clinically meaningful alterations in the pharmacokinetics of rosiglitazone, a probe CYP2C8 substrate, following coadministration of multiple‐dose LRPT in healthy subjects. Therefore, findings suggest that LRPT does not inhibit CYP2C8‐mediated metabolism.