Evaluation of Pepsinogen I as a Biomarker of Drug-induced Gastric Mucosal Injury in Cynomolgus Monkeys

• Published in: Toxicologic pathology Vol. 45; no. 2; p. 296
• Main Authors: Ennulat, Daniela, Lynch, Karen M, Kimbrough, Carie L, Mirabile, Rosanna C, Rehm, Sabine
• Format: Journal Article
• Language: English
• Published: United States 01.02.2017
• Subjects: Animals; Biomarkers - blood; Drug Evaluation, Preclinical - standards; Drug Evaluation, Preclinical - veterinary; Drug-Related Side Effects and Adverse Reactions - blood; Female; Gastric Mucosa - drug effects; Gastric Mucosa - injuries; Macaca fascicularis; Male; Pepsinogen A - blood; Retrospective Studies; Toxicity Tests - standards; Toxicity Tests - veterinary; stomach; monkey; biomarker; pepsinogen I
• ISSN: 1533-1601
• DOI: 10.1177/0192623316678696

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.