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  • Title: Effects of laropiprant, a selective prostaglandin D(2) receptor 1 antagonist, on the pharmacokinetics of rosiglitazone.
    Author: Schwartz JI, Stroh M, Gao B, Liu F, Rosko K, Zajic S, Meehan AJ, Ruckle J, Lai E, Wagner JA.
    Journal: Cardiovasc Ther; 2009; 27(4):239-45. PubMed ID: 19903187.
    Abstract:
    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-infinity) 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.
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