Effects of intravenous infusion, vest wearing and repeated intravenous blood collection on clinical pathology parameters in cynomolgus monkeys (Macaca fascicularis).

Abstract

Nonhuman primates are used extensively in a variety of nonclinical safety evaluation studies of new drugs. In those studies, intravenous infusion is a common treatment method, a noninvasive telemetry system is usually used for cardiovascular safety and pharmacology evaluation, and blood samples are repeatedly collected for various analysis. Intravenous infusion, vest wearing, and repeated intravenous blood collection can caused a stress response in cynomolgus monkeys, which may lead to changes in clinical pathology parameters in them. Here, we aimed to test the effects of the above operations on clinical pathology parameters in cynomolgus monkeys. Twenty monkeys (10 male/10 female) were administered 0.9% sodium chloride injections via intravenous infusions on Days 1 and 10. Each animal wore a vest before each dosing, and the vest was removed at 24 h after each dosing. Blood samples were collected before the first dose and at 2 min, 24 h, 48 h, 72 h, and 168 h after each dosing. As compared to values before the first dose (D-1) increases in reticulocytes (percentage and absolute count) and decreases in erythrocytes (red blood cells, hemoglobin, and hematocrit) were noted after dosing. The decrease in erythrocytes and increase in reticulocytes were considered to the related to the repeated intravenous blood collection. Increases in leukocytes (white blood cells and absolute count and percentage of neutrophils) and platelets (mean platelet volume and platelet distribution width) were noted at 2 min or 24 h post dose. Increases in aspartate aminotransferase, direct bilirubin, creatine kinase, C-reactive protein, and human cardiac troponin I and decreases in inorganic phosphate were noted at 2 min to 72 h post dose.