A subchronic intravenous toxicity study of magnesium fructose-1,6-diphosphate in beagle dogs.
Magnesium fructose-1,6-diphosphate is a novel agent of antimyocardial ischaemia. In the present study, the subchronic toxicity of magnesium fructose-1,6-diphosphate was investigated after 13-week repeated intravenous administration in beagle dogs. The animals received doses of 0, 75, 150 and 300 mg/kg/day (three males and three females for each dose). During the study period, clinical signs, mortality, body weights, food consumption, electrocardiogram, urinalysis, haematology, clinical biochemistry, macroscopic findings, organ weights and histopathology were examined. The administration of magnesium fructose-1,6-diphosphate resulted in increased incidence of clinical signs, including salivation and emesis. These effects were transient and were noted in almost all dogs given 300 mg/kg/day and occasionally noted in the 150 mg/kg/day dose-treated animals. Serum magnesium in the 150 mg/kg/day and 300 mg/kg/day dose-treated animals was significantly increased after 6- and 13-week administration, but recovered at the end of a 2-week recovery period. At 6 weeks, a statistically significant decrease in serum electrolytes, including sodium and potassium, was observed in the treatment groups. There were no other treatment-related findings. Under the conditions of the present study, magnesium fructose-1,6-diphosphate did not show any evidence of target organ toxicity. The no-observed-adverse-effect level for 13-week intravenous administration of magnesium fructose-1,6-diphosphate to beagle dogs was considered 75 mg/kg/day based on observations of clinical signs and serum electrolytes.
Wang
Meng
M
State Key Laboratory of Materials-Oriented Chemical Engineering, Jiangsu Provincial Institute of Materia Medica, Nanjing University of Technology, Nanjing, China. mengwang.drug@hotmail.com
Yao
Jun
J
Chen
Jia-Ying
JY
Bai
Wen-Xia
WX
Mei
Sheng-Yao
SY
Pan
Wei-Na
WN
Pan
Yu-Ying
YY
Yu
Fei-Long
FL
D000818:Animals; D002317:Cardiovascular Agents / Q000097:blood / Q000737:chemistry / Q000633:toxicity*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D005635:Fructosediphosphates / Q000097:blood / Q000737:chemistry / Q000633:toxicity*; D007275:Injections, Intravenous; D007928:Lethal Dose 50; D008274:Magnesium / Q000097:blood / Q000737:chemistry / Q000633:toxicity*; D008297:Male; D020714:Maximum Tolerated Dose; D036401:Toxicity Tests, Chronic
D002317:Cardiovascular Agents; D005635:Fructosediphosphates; D008274:Magnesium; C029063:fructose-1,6-diphosphate