Effects of laropiprant, a selective prostaglandin D(2) receptor 1 antagonist, on the pharmacokinetics of rosiglitazone.
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.
Schwartz
Jules I
JI
Merck & Co., Inc., Rahway, NJ 07065, USA.
Stroh
Mark
M
Gao
Bing
B
Liu
Fang
F
Rosko
Kimberly
K
Zajic
Stefan
S
Meehan
Alan J
AJ
Ruckle
Jon
J
Lai
Eseng
E
Wagner
John A
JA
D000328:Adult; D018592:Cross-Over Studies; D004347:Drug Interactions; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000493:pharmacokinetics*; D007211:Indoles / Q000494:pharmacology*; D008875:Middle Aged; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors*; D011982:Receptors, Prostaglandin / Q000037:antagonists & inhibitors*; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000493:pharmacokinetics*
D007004:Hypoglycemic Agents; D007211:Indoles; C518174:MK-0524; D011971:Receptors, Immunologic; D011982:Receptors, Prostaglandin; D045162:Thiazolidinediones; D000077154:Rosiglitazone; C036293:prostaglandin D2 receptor