Comparison of Standard Clinical Pathology Parameter Values in Fasted and Fed Rats and Non-human Primates

Abstract

The impact of non-fasting on clinical pathology parameters in pharmacologic safety assessment has been incompletely characterized. The aim of this study was to characterize changes in hematology, coagulation, and clinical chemistry parameters between healthy fasted and fed rats and macaques. Adult Sprague-Dawley rats (41 males, 40 females) and cynomolgus macaques (10 per sex) were sampled after free access to food and after 8 hours of fasting. Fed rats demonstrated lower reticulocyte and neutrophil counts in males only. Higher alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase activities and higher glucose, triglyceride, cholesterol, and globulin concentrations were observed with lower urea nitrogen, albumin, and phosphorus concentrations in fed compared with fasted rats of both sexes. Fed macaques of both sexes demonstrated higher triglyceride concentrations and lower phosphorus and total bilirubin concentrations. All changes in fed compared with fasted rats and macaques were considered minor. Non-fasting did not impact coagulation parameters in rats and macaques or hematology parameters in macaques. This study supports that non-fasting has a minimal impact on standard clinical pathology parameters in Sprague-Dawley rats and cynomolgus macaques; however, fasting is still recommended when there are anticipated effects on glucose and lipid metabolism or on endocrine systems related to energy metabolism.