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

抄録

Nonhuman primates are used extensively in a variety of non-clinical safety evaluation studies of new drugs. In those studies, intravenous infusion is a common treatment method, non-invasive telemetry system is usually used for cardiovascular safety and pharmacology evaluation, and blood samples are repeated collected for various analysis. Intravenous infusion, vest wearing and repeated bleeding can caused the stress response in cynomolgus monkeys, which may lead to changes on clinical pathology parameters in cynomolgus monkeys. Here, we aimed to test the effectiveness of the above operations on clinical pathology parameters in cynomolgus monkeys. 0.9% sodium chloride injection was administrated to 20 monkeys (10 animals/sex) via intravenous infusion on Day 1 and Day 10. Each animal wore the vest before each dosing, the vest was removed at 24 hr after each dosing. Blood samples were collected pre-dosing, at 2 min, 24 hr, 48 hr, 72 hr, and 168 hr after each dosing. As compared to the pre-dosing (D -1) values, increased reticulocytes (RET% and RET#) and decreased erythrocytes (RBC, HGB, and HCT) were noted after dosing. The loss of erythrocytes and increases of reticulocytes were considered to the related to the repeated bleeding. Increased leukocytes (WBC, NEUT#, and NEUT%) and platelets (MPV and PDW) were noted at 2 min or 24 hr post dose. Increased AST, DBIL, CK, CRP, and hsTnI and decreased P were noted at 2 min to 72 hr post dose.