Podpletnya O. The analysis of pharmacological activity and safety of nonsteroidal anti-inflammatory drugs and experimental ground of anti-inflammatory and analgesic therapy improvement

Thesis is devoted to complex investigation of pharmacologic activity of new combined drug "Indotril" which contains indometacin in subthreshold dose and thiotriazolin (1:3). Research includes the experimental ground of indometacin and thiotriazolin combination rationality in conditions of different inflammatory models and pain syndromes, acute and chronic toxicity of combined drug investigation, the comparative analysis between investigated drug and other effective compositions of nonsteroidal anti-inflammatory drugs (NSAIDs) with antioxidants and chondroprotectors as well as with modern representatives of NSAIDs in conditions of adjuvant arthritis and arthrosis models in animals (rats). Combined drug - tablets "Indotril" was established to excel other investigated NSAIDs and their combinations with antioxidants and chondroprotectors on analgesic (visceral and somatic pain) and anti-inflammatory activity in conditions of aseptic inflammation with using of different inflammatory agents due to synergeticaction of components: powerful indometacin's anticyclooxygenase effect and antioxidant, membrane stabilizing, antiischemic and anti-inflammatory effect of thiotriazolin. Combined using of indometacin and thiotriazolin (1:3) is 4,7 times less toxic than indometacin's substance after single-dose introduction. The investigated drug demonstrated good safety profile during chronic administration: "Indotril" doesn't influence on glomerular tissues of kidneys and less than indometacin and diclofenac sodium retains electrolytes in the body; unlike classical NSAIDs - indometacin and diclofenac sodium - doesn't have cholestatic, expressed hematotoxic, gastrotoxic and chondrotoxic activity. The study of specific pharmacological activity confirms advantages of "Indotril" over other investigated drugs in symptoms reducing and some pathogenetic effectiveness availability in inflammatory and destructive joint disease treatment.