摘要
目的:考察连续给予脯氨酰羟化酶抑制剂鲁非罗尼(LF)对实验动物的毒性反应。方法:对SD大鼠和Beagle犬连续口服给药6个月,进行常规观察并测定血清和组织中的羟脯氨酸含量。结果:IF在2500mg·kg^(-1)·d^(-1)剂量时使大鼠尿素氮(BUN)升高,总蛋白(TP)和白蛋白(ALB)降低,血清和肝脏羟脯氨酸含量降低,肝、肺和肾重量系数增加;50和350mg·kg^(-1)·d^(-1)剂量对大鼠各项指标无明显影响。LF 50,150和450mg·kg^(-1)·d^(-1)剂量对犬各项指标无明显影响。结论:LF安全剂量高,仅在极高剂量才引起可逆性毒性反应。
Objective: To observe the long-term toxicity of lufironil (LF, pyridine-2, 4-dicar-boxylic-di(2-methoxy-ethyl)amide) ,a competitive inhibitor of prolylhydroxylase, in animals. Methods: SD rats and Beagle dogs were administered orally various doses of LF for 6 months. Hydroxyproline (Hyp) assay in serum and tissue were made besides routine examinations.Results:LF reduced TP,AL and Hyp in serum and tissue, increased BUN and the weight indexes of liver, kidney and lung in the rats treated with daily dose of 2500mg·kg-1.But no significant changes of the above parameters were seen in the rats treated with 50 and 350mg·kg-1 . All the tested parameters remained normal in the dogs treated with daily doses of 50,150 and 450mg·kg-1.Conclusion:LF expresses a high safe dosage range and its reversible toxicity only occurs in extremely high dose.
出处
《中国新药杂志》
CAS
CSCD
北大核心
2003年第9期718-720,共3页
Chinese Journal of New Drugs
基金
原国家医药管理局重点项目(编号:93-创-05)
