Evaluation of Pepsinogen I as a Biomarker of Drug-induced Gastric Mucosal Injury in Cynomolgus Monkeys.
Toxicol Pathol
; 45(2): 296-301, 2017 02.
Article
em En
| MEDLINE
| ID: mdl-28007014
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.
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Base de dados:
MEDLINE
Assunto principal:
Testes de Toxicidade
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Pepsinogênio A
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Avaliação Pré-Clínica de Medicamentos
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Mucosa Gástrica
Tipo de estudo:
Observational_studies
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Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article