Laropiprant is a selective antagonist of the prostaglandin D2 (PGD2) 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 900mg and multiple doses up to 450mg were generally well tolerated. Laropiprant exhibited dose-proportional pharmacokinetics. Oral absorption is rapid (Tmax=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 6mg and higher were effective in suppressing PGD2-induced cyclic AMP accumulation in platelets, demonstrating laropiprant target engagement with DP1. Laropiprant has detectable offtarget antagonist effects at the thromboxane A2 receptor but no clinically significant effect on collagen-induced platelet aggregation or bleeding times with multiple doses up to 200mg.