Study of PEG-Filstim sub-acute toxicity

Abstract

Febrile neutropenia caused by cytostatic therapy in the treatment of oncological diseases is a frequent complication, which results in enforced reduction in chemotherapy doses and lower effectiveness of the treatment. Introduction of the recombinant forms of the natural protein granulocyte colony-stimulating factor into clinical practice has allowed to minimize the negative consequences of myelosuppressive therapies. The main task of repeated dose toxicity studies of drugs is evaluation of damaging effects of the pharmacological substance, revealing the most sensitive organs and systems in the body.
 Therefore, our work was aimed at studying sub-acute toxicity of PEG-Filstim.
 Toxicity study of PEG-Filstim was performed in 50 white wild-type rats of both sexes with body weight 170 to 230 g on daily (28 days) subcutaneous administration in the doses of 0.5, 1.0 and 2.0 mg/kg. During the whole observational period, survival, water and food consumption, body weight and symptoms of intoxication were registered. After completion of the experiment, spontaneous diurnal diuresis was evaluated and clinical blood and urine examination performed in all groups of animals.
 The results have shown that PEG-Filstim on daily subcutaneous administration in the doses of 0.5, 1.0 and 2.0 mg/kg during 28 days does not cause death in the animals, nor general toxic effects on health, behaviour, food and water consumption, body weight growth in laboratory rats. Upon repeated administration in the studied doses, PEG-Filstim does not affect protein, lipid, carbohydrate metabolism, does not impair functions of urinary and hepatobiliary systems, but increases blood serum alkaline phosphatase activity. PEG-Filstim causes development of pronounced neutrophil leucocytosis and increase in monocyte, lymphocyte and eosinophil count. In the maximum dose of 2.0 mg/kg the studied drug decreases blood red cell count and haemoglobin level.