Tymchenko O. Pharmacological rationale of advisability of creation of new medicines of naloxone and ketorolac as nasal sprays

The thesis is devoted to experimental pharmacological rationale of creation new naloxon and ketorolac medicines in dosage form as nasal sprays for increasing of efficiency and safety of emergency for opioid overdose and pain syndrome, respectively. The pharmacokinetics of naloxone in rabbits when administered intranasally was investigated and experimentally substantiated the optimal content of naloxone nasal spray – 1,2 % and its dose – 1,2 mg. It has been proved that the developed nasal spray of ketorolac has an advantage of ketorolac bioavailability comparatively with the nasal spray SPRIX® ( «Roxro Pharma», USA) by 1,3 times. The severity of the specific pharmacological activity of ketorolac and naloxone in rats after intranasal administration was investigated, which were, respectively, equal to 78,8-103,3% and 79,4-89,1% comparatively to their effects when administered intramuscularly. The safety profile of naloxone and ketorolac intranasal administration to laboratory animals was established. It has been proved a good intranasal tolerability of naloxon anf ketorolac and absence of significant local irritating action of their repeated instillations.