Muzyka V. Pharmacological dynamics and pharmacological kinetics of combined antibacterial medicinal product containing florfenicol and flunixin meglumin

The materials of the thesis are devoted to the development of new complex antimicrobial medicinal product containing florfenicol and flunixin meglumin and the studying of its pharmacological dynamics and pharmacological kinetics as one source of prevention of antibiotic resistance development of microorganisms. The optimal therapeutic dose of combined medicinal product was determined for the treatment of young cattle and pigs suffering from acute respiratory diseases (intramuscular administration): 20 mg of florfenicol and 2.2 mg of flunixin meglumin per 1 kg of bodyweight twice with time sequence of 48 hours. The administration of flunixin meglumin in complex antibacterial medicinal product containing florfenicol improved the clinical response that facilitated the recovery of animals in comparison of the application of mono medicinal product containing florfenicol. At addition of flunixin meglumin to preparation from florfenicol clinical indexes got better and recovery of animals came quicker, by comparison to application of mono medicinal product containing florfenicol. During the studying of pharmacological dynamics of florfenicol the primary attention is paid to hematological changes (erythropenia, anemic phenomena etc.). It was determined that under conditions of oral administration to rats and mice the DL50 of florfenicol is equal to 3750 (2778±4722) and 9100 (7962±10238) mg/kg of bodyweight. According to GOST 12.1.007-76 florfenicol belongs to the 4th class of toxicity, it does not cause irritating and dermonecrotic effect. Taking into account the analysis of hematologic, biochemical indices and the results of pathomorphological tests of internal organs it was determined that the dose of florfenicol of 420 mg/kg (1/10 of DL50) is toxic; the dose of 210 mg/kg (1/20 of DL50) is threshold one; the dose of 84 mg/kg (1/50 of DL50) is non-active. The studying of pharmacological kinetics peculiarities of florfenicol and flunixin meglumin in pigs after intramuscular administration of florfenicol showed that maximum concentration of antibiotic in blood was observed in 2,5 hours. The therapeutic antibacterial concentration remains in organs and tissues of animals during 48 hours. The concentration of flunixin meglumin was determined during 4 hours. The withdrawal period was equal to 1,66 hours. The average meaning of kinetic volume constituted 0,52 l that demonstrates the circulation of the medicinal product. On the basis of conducted tests the positive influence of floricol administered in recommended therapeutic was demonstrated. The general clinical and morphological organism condition was satisfactory. The studied medicinal product is safe and non-toxic, namely tolerant for young cattle and pigs.