Proglumide is an orally administered
cholecystokinin receptor antagonist that was found to improve
nonalcoholic steatohepatitis, reverse
liver fibrosis, and decrease incidence of
hepatocellular carcinoma (HCC) in animal models. The current investigation aimed to test the pharmacokinetics and safety of
proglumide in subjects with hepatic impairment compared with healthy controls. In this translational study, subjects with confirmed
cirrhosis, Child-Pugh stage A or B, or healthy controls were recruited for a single-dosing study. Baseline urine and blood samples were obtained before administration of
proglumide and also collected after ingestion up to 24 h.
Drug concentrations measured by mass spectroscopy revealed peak plasma concentrations (Cmax) of 7847, 9721, and 10,635 ng/mL at about 1 h (Tmax) for healthy controls, subjects with Child-Pugh A, and B
cirrhosis, respectively. The serum elimination half time was 3 h. Maximum urine
drug concentration (Cmax = ~411 µg/mL) was observed at 3 h, and urinary
drug concentration declined at 5 h. There were no adverse events reported, and follow-up liver panels in
cirrhosis subjects were unchanged or improved. This investigation demonstrated that
proglumide is safe and has similar pharmacokinetic properties in subjects with
cirrhosis as in healthy controls; therefore, it will be safe to test the efficacy of
proglumide as a therapeutic agent in those subjects with
cirrhosis or HCC.