PDF(Pubmed)
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.
摘要：
非人灵长类动物被广泛用于各种新药的非临床安全性评价研究中。在这些研究中,静脉输液是一种常见的治疗方法,无创遥测系统通常用于心血管安全性和药理学评估，和血液样本被重复收集用于各种分析。静脉输液,穿背心和反复出血可引起食蟹猴的应激反应，这可能导致食蟹猴临床病理参数的变化。这里,我们旨在测试上述手术对食蟹猴临床病理参数的有效性。在第1天和第10天通过静脉内输注对20只猴子(10只动物/性别)施用0.9%氯化钠注射液。每只动物在每次给药前都穿着背心，在每次给药后24小时取出背心。给药前收集血样，在2分钟，24小时,48小时,72小时,和每次给药后168小时。与给药前(D-1)值相比，网织红细胞增加(RET%和RET#)和红细胞减少(RBC，HGB,和HCT）在给药后记录。红细胞的丢失和网织红细胞的增加被认为与反复出血有关。增加的白细胞（白细胞，NEUT#,和NEUT%）和血小板（MPV和PDW）在给药后2分钟或24小时记录。增加AST,DBIL,CK,CRP,在给药后2分钟至72小时观察到hsTnI和降低的P。
