[Pharmacology and toxicology of etofylline clofibrate]

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.