EXPERIMENTAL STUDY OF THE SPECIFIC PHARMACOLOGICAL ACTIVITY OF THE DRUG PEG-FILSTIM

Abstract

The aim of the work: to study the specific pharmacological activity of the drug PEG-Filstim on the febrile neutropenia model in mice. 

Materials and Methods. Experimental leukopenia in male C57BL/6 mice was modeled by single intraventricular administration of cyclophosphamide at a dose of 250 mg/kg. PEG-Filstim or reference drug Neulastim were administered subcutaneously once in the dose of 1 mg/kg 24 hours after the injection of cyclophosphamide, or 24 hours after the injection of 0.9 % sodium chloride solution. On the 7th day after administration of studied and reference drugs, the animals were anesthetized and blood from the orbital sinus was collected for smear preparation and white blood cells counting.
After euthanasia of animals the marrow from the right thigh-bone was washed-out, and general number of myelocariocytes was counted. A myelogram, leukocyte: erythrocyte ratio and neutrophil maturation index were counted in the bone marrow smear.

Results and Discussion. The results of the study has shown, that in healthy mice after single subcutaneous administration of PEG-Filstim or Neulastim an increase in the number of white blood cells is observed, as compared to the intact controls.

In the animals with experimental leukopenia, under action of the studied and reference drugs the absolute number of leukocytes also increased, as compared to the control 2 (animals with experimental pathology). Furthermore, the effects of PEG-Filstim or Neulastim on this parameter did not have statistically significant differences. As the results of our studies show, both in healthy mice and in the animals with experimental leukopenia, single administration of the drugs PEG-Filstim or Neulastim increases the number of the myelocariocytes in the bone marrow. Incidentally, this increase was not in relation with changes in the absolute content of undifferentiated blasts, eosinophils, monocytes and immature forms of neutrophils.

Both in healthy mice and in the animals with experimental pathology, after administration of the studied or reference drugs an increase was observed in absolute content of mature forms (bands and segments) of neutrophils. Those changes resulted in a decrease in neutrophil maturation index.

Conclusions. The drug PEG-Filstim at the dose of 1 mg/kg possesses a pronounced hemostimulative effect both in intact mice, and in animals with experimental leukopenia. Under the action of the drug, the number of white blood cells in peripheral blood increases (by increasing the number of band neutrophils and lymphocytes), and also increases the number of myelocariocytes in the bone marrow (by increasing the number of mature neutrophils, basophils of all generations, and erythrocariocytes). By its characteristics, the studied drug is highly competitive with the reference product Neulastim.