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 D(2) 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).
Wang
Ying-Hong
YH
Merck Research Laboratories, West Point, Pennsylvania, USA.
Liu
Fang
F
Luk
Julie Ann Mabalot
JA
Nirula
Ajay
A
Johnson-Levonas
Amy O
AO
Lasseter
Kenneth C
KC
Marbury
Thomas C
TC
Lunde
N Martin
NM
Wagner
John A
JA
Lai
Eseng
E
D005260:Female; D005483:Flushing / Q000139:chemically induced / Q000517:prevention & control; D006207:Half-Life; D048550:Hepatic Insufficiency / Q000378:metabolism*; D006801:Humans; D007211:Indoles / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D009525:Niacin / Q000009:adverse effects; D020033:Protein Isoforms / Q000037:antagonists & inhibitors; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors*; D011982:Receptors, Prostaglandin / Q000037:antagonists & inhibitors*; D012720:Severity of Illness Index
D007211:Indoles; C518174:MK-0524; D020033:Protein Isoforms; D011971:Receptors, Immunologic; D011982:Receptors, Prostaglandin; D009525:Niacin; C036293:prostaglandin D2 receptor