PHARMACOKINETIC PROFILES OF THE ANALGESIC DRUG FLUPIRTINE IN DOGS AFTER THE ADMINISTRATION OF FOUR PHARMACEUTICAL FORMULATIONS

Objective Flupirtine (FLU) is a non-opioid analgesic drug with no antipyretic or anti-inflammatory effects, used in the treatment of a wide range of pain states in humans. There is a substantial body of evidence on the efficacy of FLU in humans, however this is inadequate to recommend its off-label use in veterinary clinical practice. The aim of this study was to evaluate the pharmacokinetic profiles of FLU after intravenous (IV), oral (PO) immediate release (IR) and prolonged release (PR) and rectal (RC) administrations in healthy dogs. Study design four-treatment, single-dose, four-phase, unpaired, cross-over design (4x4 Latin-square). Animals Six Labrador breed adult dogs. Methods Animals in groups 1, 2 and 4 received a single dose of 5 mg kg-1 FLU administered by IV, POIR and RC routes. Group 3 received a single dose of 200 mg subject-1 via the POPR route. The wash out periods were 1-week. Blood samples (1 mL) were collected at assigned times up to 48 hours and plasma was then analysed by a validated HPLC method. Results Adverse effects including salivation, tremors and vomiting were noted in the IV group, however these did not occur in the extravascular groups. They resolved rapidly (10 min) and spontaneously. The FLU plasma concentrations were detectable in all the treatment groups up to 36 h following treatment. The extravascular pharmacokinetic profiles showed similar trends. The bioavailability values after POIR, POPR and RC were 41.9, 36.8 and 29.3%, respectively. Surprisingly, POIR and POPR administrations showed no significant differences in pharmacokinetic profiles and parameters. A 5 mg kg-1 POIR dose or a 200 mg subject-1 POPR dose gave plasma concentrations similar to those reported in humans after clinical dosing. Conclusion and clinical relevance This study represents the first step which should pave the way for use of this active ingredient in canine medicine.