Body weight loss without reduction in food consumption observed in cynomolgus monkeys during non-clinical toxicity studies

在非临床毒性研究中,食蟹猴观察到体重减轻但食物摄入量并未减少。

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Abstract

In pharmaceutical development, weight loss is occasionally observed in monkeys during non-clinical toxicity studies and can be difficult to differentiate from drug effects. This study retrospectively analyzed data from control group monkeys without drug treatment to investigate the incidence of weight loss and its physiological and pathological characteristics. We also investigated potential improvements through enhanced animal welfare. In the 4- and 13-week toxicity studies conducted at the test facility from 2010 to 2022, 684 control group monkeys were investigated. Among them, 3 animals in the 4-week toxicity studies and 5 animals in the 13-week toxicity studies showed a weight change rate of less than -10%, resulting in an incidence rate of 1.2%. However, these animals had adequate food consumption. Animals in the 4-week toxicity studies showed signs of stress in histopathology. Additionally, 2/3 animals in the 4-week toxicity studies had decreased blood glucose levels and 1/5 animal in the 13-week toxicity study fell into a crouching posture, suggesting hypoglycemia that was alleviated with glucose administration, indicating stress-induced metabolic abnormalities. From 2015, an enrichment program was implemented to improve animal welfare. Prior to this program, 2.4% of animals showed a weight change rate of less than -10%, which dropped to 0.25% post-implementation, suggesting the program's effectiveness in reducing stress. These results clarify the characteristics of animals that lose weight during toxicity studies and suggest that improving animal welfare can reduce the incidence rate.

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