Nonclinical toxicology studies with sodium taurodeoxycholate: acute and subacute toxicity in dogs

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Title
Nonclinical toxicology studies with sodium taurodeoxycholate: acute and subacute toxicity in dogs
Author(s)
H J Choi; J W Yun; Y H Kim; E Kwon; M K Hyon; J Y Kim; J H Che; J S Park; Hyoung-Chin Kim; W H Kim; S Y Seong; B C Kang
Bibliographic Citation
Drug and Chemical Toxicology, vol. 44, no. 2, pp. 161-169
Publication Year
2021
Abstract
Sodium taurodeoxycholate (TDCA) has been investigated for various inflammatory disorders such as sepsis. We recently evaluated nonclinical safety profile of TDCA using rats infused intravenously. As a series of preclinical safety investigations, we further conducted toxicity studies with TDCA delivered to dogs via intravenous administration under Good Laboratory Practice regulation in this study. In dose range-finding study (dose escalation study), dogs given with TDCA at a dose of 150 mg/kg showed marked changes in clinical signs, hematology, and serum biochemistry. And biochemical markers of liver damage and local skin lesions were observed following intravenous infusion of 100mg/kg TDCA, suggesting that 100mg/kg was chosen as the highest dose of TDCA for 4-week repeated-dose toxicity study using dogs. Despite no treatment-related significant changes in body weight, food consumption, ophthalmoscopy, and urinalysis, skin lesions were observed at the injection site of animals administered with higher than 50mg/kg of TDCA along with biochemical and histopathological changes associated with liver injury. However, most of off-target effects were found to be reversible since these were recovered after stopping TDCA infusion. These findings indicate that the no-observed-adverse-effect-level (NOAEL) for TDCA in dogs was considered to be 5mg/kg/d. Taken together, our results provide important toxicological profiles regarding the safe dose of TDCA for drug development or clinical application.
Keyword
TaurodeoxycholateAcute toxicityBile acidDogSepsisSubacute toxicity
ISSN
0148-0545
Publisher
T&F (Taylor & Francis)
DOI
http://dx.doi.org/10.1080/01480545.2019.1566352
Type
Article
Appears in Collections:
Ochang Branch Institute > Division of Bioinfrastructure > 1. Journal Articles
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