Dose-dependent acute liver injury with hypersensitivity features in humans due to a novel microsomal prostaglandin E synthase 1 inhibitor.

ABSTRACT:

Aims

LY3031207, a novel microsomal prostaglandin E synthase 1 inhibitor, was evaluated in a multiple ascending dose study after nonclinical toxicology studies and a single ascending dose study demonstrated an acceptable toxicity, safety and tolerability profile.

Methods

Healthy subjects were randomized to receive LY3031207 (25, 75 and 275 mg), placebo or celecoxib (400 mg) once daily for 28 days. The safety, tolerability and pharmacokinetic and pharmacodynamic profiles of LY3031207 were evaluated.

Results

The study was terminated when two subjects experienced drug-induced liver injury (DILI) after they had received 225 mg LY3031207 for 19 days. Liver biopsy from these subjects revealed acute liver injury with eosinophilic infiltration. Four additional DILI cases were

SUBMITTER: Jin Y 

PROVIDER: S-EPMC5736846 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature