Evaluation of Pepsinogen I as a Biomarker of Drug-induced Gastric Mucosal Injury in Cynomolgus Monkeys
| العنوان: | Evaluation of Pepsinogen I as a Biomarker of Drug-induced Gastric Mucosal Injury in Cynomolgus Monkeys |
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| المؤلفون: | Sabine Rehm, Karen M. Lynch, Daniela Ennulat, Rosanna C. Mirabile, Carie L. Kimbrough |
| المصدر: | Toxicologic Pathology. 45:296-301 |
| بيانات النشر: | SAGE Publications, 2016. |
| سنة النشر: | 2016 |
| مصطلحات موضوعية: | Male, 0301 basic medicine, medicine.medical_specialty, Pathology, Drug-Related Side Effects and Adverse Reactions, Pepsinogen A, Drug Evaluation, Preclinical, Biology, Toxicology, Gastroenterology, Pathology and Forensic Medicine, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Toxicity Tests, medicine, Gastric mucosa, Animals, Molecular Biology, Retrospective Studies, Receiver operating characteristic, medicine.diagnostic_test, Stomach, Area under the curve, Cell Biology, Fold change, Macaca fascicularis, 030104 developmental biology, medicine.anatomical_structure, Gastric Mucosa, Immunoassay, Biomarker (medicine), Female, 030211 gastroenterology & hepatology, Biomarkers |
| الوصف: | 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. |
| تدمد: | 1533-1601 0192-6233 |
| DOI: | 10.1177/0192623316678696 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::33c722efd7d4b95a17b6562c424e972a https://doi.org/10.1177/0192623316678696 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....33c722efd7d4b95a17b6562c424e972a |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15331601 01926233 |
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| DOI: | 10.1177/0192623316678696 |