Host: The Japanese Society of Toxicology
Name : The 51st Annual Meeting of the Japanese Society of Toxicology
Date : July 03, 2024 - July 05, 2024
Gastrointestinal toxicity in non-clinical studies is identified in abnormal clinical signs such as vomiting and diarrhea, changes in body weight and food intake, and macro/microscopic findings. It is needed to consider differences of the function and histological structure from the stomach to the rectum, the turnover rate of mucosal epithelial cells, and intestinal flora between animal species when drug candidates are evaluated.
Different susceptibility in animal species sometimes becomes an issue in drug development process. It has been known that the presence/absence of abnormal feces and the degree of histopathological changes are different in species even treated with the same compound. Particularly, higher susceptibility of non-rodents including histopathological grades compared with rats is sometimes experienced, and it can significantly affect the estimation of safety margin in humans. Additionally, the cause of gastrointestinal toxicity by antibiotics is mainly thought to be malabsorption due to a decrease in intestinal flora, but the composition of intestinal flora has species differences. Antibacterial effects of drugs on the intestinal flora is also considered to be varied in animal species. It is important to be aware of these backgrounds when discussing extrapolation to humans.
In contrast, there is little knowledge regarding juvenile or aged animals. The age of animals used in toxicity study is different depends on the age of the target patient population. However, for compounds indicated for adults aged 18 and above, the age of animals used is generally uniform. Reports investigating age-related differences in the profile of changes between juvenile and aged animals is rare.
In this presentation, species differences of gastrointestinal toxicity profile including histopathology in animal species will be summarized.
