13-甲基肉豆蔻酸对Beagle犬的长期毒性研究

Long-term toxicity study of 13-methyltetradecanoic acid in Beagle dogs

目的:评价13-甲基肉豆蔻酸(13-MTD)由于积蓄而对Beagle犬机体产生的毒性反应和其严重程度,确定无毒反应剂量,为拟定人用剂量提供参考。方法:Beagle犬12只,随机分为0.4g.kg-1和0.8g.kg-12个剂量组和空白对照组,每组4只,♀♂各半。每天口服1次,连续3个月(每周日停1d)后检查各剂量组犬的一般情况、心电图、血象、肝肾功能、尿常规及病理检验等指标并进行恢复性观察。结果:各剂量组犬的各项指标均无明显异常,停药半个月观察未见13-MTD延迟性不良反应。结论:13-MTD以0.8g.kg-1相当于临床拟用量40倍给予Beagle犬连续口服3个月,无明显毒性反应。

OBJECTIVE To monitor toxic reactions and seriousness due to long-term accumulation of drug in the body of Beagle dogs after twelve-week oral administration of 13 methyltetradecanoic acid （13-MTD）, for reference in clinical trials. METHODS Twelve Beagle dogs were randomly divided into 3 groups of 4 with 2 in each gender. The dogs in two test groups were orally administered with 13-MTD at 0. 4 g. kg ^-1 and 0. 8 g.kg^-1 daily for twelve weeks, respectively. RESULTS No significant anomalies were found in the animals in test groups, comparing to those in the control group, including electrocardiogram, hemogram, hepatorenal functions, routine examination of urine, and pathological biopsy. Another 2-week observation after the end of treatment also showed no delayed abnormal reactions. CONCLUSION Oral administration of 13-MTD 0. 8 g. kg^-1 （40 times clinically recommended dose） daily for twelve weeks in beagle dogs was safe.