Sterner W, Korn W D
Arzneimittelforschung. 1980;30(11b):2023-31.
1-(Theophyllin-7-yl)-ethyl-2-[2-(p-chlorophenoxy)-2-methylpropionate] (etofylline clofibrate, ML 1024, Duolip) was investigated in acute and chronic toxicity studies, using oral application. In addition studies in reproduction toxicology and safety pharmacology were performed. Under the conditions of the experiments the following important findings were observed: In the acute toxicity studies ML 1024 showed a dose-dependent symptomatology in all three species (rat, mouse, dog) used, no late mortalities occurred. As compared to the reference substances clofibric acid, clofibrate and etofylline, ML 1024 showed a considerably lower toxicity. The chronic studies over 6 months in mini-pigs and rats revealed that the liver was the target organ in both species. ML 1024 influenced the reproduction performance of the male and female rat. However, toxic dose levels were necessary to achieve those effects. In the teratogenic studies no teratogenic but some fetotoxic effects in the high dose level were observed. No effects could be observed in the peri- and postnatal experiment. The pharmacodynamic studies did not reveal any significant functional influences of ML 1024 on the major organs and organ systems.
1-(茶碱-7-基)-乙基-2-[2-(对氯苯氧基)-2-甲基丙酸酯](益多酯，ML 1024，多利平)通过口服给药进行了急性和慢性毒性研究。此外，还进行了生殖毒理学和安全药理学研究。在实验条件下，观察到以下重要结果：在急性毒性研究中，ML 1024在所用的所有三个物种(大鼠、小鼠、狗)中均表现出剂量依赖性症状，未出现晚期死亡。与对照物质氯贝酸、氯贝特和氨茶碱相比，ML 1024的毒性明显较低。在小型猪和大鼠中进行的为期6个月的慢性研究表明，肝脏是这两个物种的靶器官。ML 1024影响雄性和雌性大鼠的生殖性能。然而，需要达到毒性剂量水平才能产生这些影响。在致畸研究中，未观察到致畸作用，但在高剂量水平观察到一些胚胎毒性作用。在围产期和产后实验中未观察到任何影响。药效学研究未发现ML 1024对主要器官和器官系统有任何显著的功能影响。
