Pharmacokinetics of Laropiprant, a Selective Prostaglandin D₂ Receptor 1 Antagonist, in Patients With Moderate Hepatic Impairment

This open-label study evaluated the influence of hepatic insufficiency on the pharmacokinetics of laropiprant (LRPT), a prostaglandin D₂ receptor-1 antagonist, to guide clinicians in the event of inadvertent dosing in patients with hepatic insufficiency. A single oral 40-mg dose of LRPT was administered to 8 patients with moderate hepatic insufficiency and 8 healthy control participants matched for important baseline characteristics. Blood samples were collected predose and up to 96 hours postdose to assess LRPT pharmacokinetics. No clinically significant effect of hepatic insufficiency would be declared if the 90% confidence interval (CI) for the estimated geometric mean ratio (GMR; hepatic insufficiency patients/ healthy participants) of AUC_0-∞ was contained within the prespecified bounds of (0.50-3.00). Estimated GMRs of AUC_0-∞ and C_max (90% CIs) were 2.78 (1.71, 4.50) and 2.17 (1.33, 3.53), respectively. The median time to C_max and apparent terminal t_1/2 of LRPT were comparable between the 2 populations (P > .100). Single-dose LPRT 40 mg was generally well tolerated in all patients. The plasma pharmacokinetics of a single 40-mg oral dose of LRPT is not similar between patients with moderate hepatic insufficiency and matched healthy participants. The GMR (90% CI) of AUC_0-∞ for patients with moderate hepatic insufficiency versus matched controls was 2.78 (1.71, 4.50).