Pharmacokinetic profiles of the analgesic flupirtine in dogs after the administration of four pharmaceutical formulations

Objective Flupirtine (FLU) is a non-opioid analgesic with no antipyretic or anti-inflammatory effects which is used in the treatment of pain in humans. There is a substantial body of evidence on the efficacy of FLU in humans but this is inadequate for the recommendation of 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 immediate release (POIR), oral prolonged release (POPR) and rectal (RC) administrations in healthy dogs. Study design Four-treatment, single-dose, fourphase, unpaired, cross-over design (4 9 4 Latinsquare). Animals Six adult Labrador dogs. Methods Animals in groups 1, 2 and 4 received a single dose of 5 mg kg1 FLU administered by IV, POIR and RC routes. Group 3 received a single dose of 200 mg subject1 via the POPR route. The washout periods were 1 week. Blood samples (1 mL) were collected at assigned times for 48 hours and plasma FLU concentrations were analysed by a validated HPLC method. Results Adverse effects including salivation, tremors and vomiting were noted in the IV group and resolved spontaneously within 10 minutes. These effects did not occur in the other groups. The FLU plasma concentrations were detectable in all of the treatment groups for 36 hours following administration. The pharmacokinetic profiles after extravascular administrations showed similar trends. The bioavailability values after POIR, POPR and RC were 41.93%, 36.78% and 29.43%, respectively. There were no significant differences in pharmacokinetic profiles between the POIR and POPR formulations. A 5 mg kg 1 POIR dose or a 200 mg subject1 POPR dose gave plasma concentrations similar to those reported in humans after clinical dosing. Conclusion and clinical relevance This study provides pharmacokinetic data that can be used to design further studies to investigate FLU in dogs.