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Pharmacokinetics, Pharmacodynamics, and Safety of a Prostaglandin D 2 Receptor Antagonist
Author(s) -
Lai E,
Wenning LA,
Crumley TM,
De Lepeleire I,
Liu F,
Hoon JN,
Van Hecken A,
Depré M,
Hilliard D,
Greenberg H,
O'Neill G,
Metters K,
Gottesdiener KG,
Wagner JA
Publication year - 2008
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/sj.clpt.6100345
Subject(s) - pharmacokinetics , pharmacology , pharmacodynamics , antagonist , tolerability , medicine , crossover study , clinical pharmacology , receptor antagonist , chemistry , placebo , receptor , adverse effect , alternative medicine , pathology
Laropiprant is a selective antagonist of the prostaglandin D 2 (PGD 2 ) receptor subtype 1 (DP1). Three double‐blind, randomized, placebo‐controlled studies evaluated the safety, tolerability, pharmacokinetics, and pharmacodynamics of single and multiple oral doses of laropiprant in healthy male volunteers. Single doses up to 900 mg and multiple doses up to 450 mg were generally well tolerated. Laropiprant exhibited dose‐proportional pharmacokinetics. Oral absorption is rapid ( T max =0.8–2.0 h) and the terminal half‐life is approximately 12–18 h. The pharmacokinetics of laropiprant was not affected by food. Single doses of 6 mg and higher were effective in suppressing PGD 2 ‐induced cyclic AMP accumulation in platelets, demonstrating laropiprant target engagement with DP1. Laropiprant has detectable off‐target antagonist effects at the thromboxane A 2 receptor but no clinically significant effect on collagen‐induced platelet aggregation or bleeding times with multiple doses up to 200 mg. Clinical Pharmacology & Therapeutics (2008); 83 , 6, 840–847 doi: 10.1038/sj.clpt.6100345