Evaluation of Pepsinogen I as a Biomarker of Drug-induced Gastric Mucosal Injury in Cynomolgus Monkeys. (February 2017)

• Record Type: Journal Article
• Authors: Ennulat, Daniela; Lynch, Karen M.; Kimbrough, Carie L.; Mirabile, Rosanna C.; Rehm, Sabine
• Other Names: Aulbach Adam guest-editor.; Jordan Holly guest-editor.; Tarrant Jacqueline guest-editor.
• Is Part Of: Toxicologic pathology. Volume 45:Number 2(2017)
• Page Start: 296
• Page End: 301
• Publication Date: 2017-02
• Subjects: monkey -- stomach -- pepsinogen I -- biomarker; Pathology -- Periodicals; Toxicology -- Periodicals; Pathology; Toxicology; 615.9
• DOI: 10.1177/0192623316678696
• Languages: English
• ISSNs: 0192-6233

Abstract

Gastric mucosal injury is frequently observed in nonclinical studies of nonhuman primates. Because microscopic evaluation of stomach is generally a terminal procedure, our objective was to determine whether serum pepsinogen I (PG I) could serve as a noninvasive biomarker for detection of gastric mucosal injury in monkey. Serum PG I was measured using a commercial human immunoassay in cynomolgus monkeys ( n = 166) prior to dosing and/or terminally in 11 studies of up to 1 month duration. Mean ( SD ) PG I values (ug/L) for monkeys with ( n = 59) and without ( n = 100) gastric mucosal degeneration were 101 (215) and 28 (12.6), respectively. For monkeys with baseline and terminal PG I data, mean ( SD ) fold change (ratio of terminal to baseline PG I) for monkeys with ( n = 57) and without ( n = 76) glandular degeneration were 4.1 (11.3) and 1 (0.28). Receiver operating characteristic area under the curve (AUC) data demonstrated moderate diagnostic accuracy for serum PG I for glandular degeneration, AUC ( SE ) 0.789 (0.04), with improved diagnostic accuracy as a fold change of baseline, AUC ( SE ) 0.816 (0.04), consistent with the large interindividual but low intraindividual variability of serum PG I values in control monkeys. These data demonstrate that serum PG I is a useful biomarker of drug-induced gastric mucosal injury in the cynomolgus monkey.