title: Pharmacokinetic profiles of the analgesic flupirtine in dogs after the administration of four pharmaceutical formulations.
abstract: 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.
  
  
  METHODS
  Four-treatment, single-dose, four-phase, unpaired, cross-over design (4×4 Latin-square).
  
  
  METHODS
  Six adult Labrador 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 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 subject(-1) POPR dose gave plasma concentrations similar to those reported in humans after clinical dosing.
  
  
  CONCLUSIONS
  This study provides pharmacokinetic data that can be used to design further studies to investigate FLU in dogs.
authors.affiliation: Department of Veterinary Sciences, University of Pisa, San Piero a Grado, Italy.
authors.forename: Virginia
authors.initials: V
authors.lastname: De Vito
authors.affiliation: Department of Pharmacology, University of Life Sciences, Lublin, Poland.
authors.forename: Beata
authors.initials: B
authors.lastname: Łebkowska-Wieruszewska
authors.affiliation: Department of Pharmacology, University of Zagazig, Zagazig, Egypt.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Shaban
authors.affiliation: Department of Animal Hygiene and Environment, University of Life Sciences, Lublin, Poland.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Lisowski
authors.affiliation: Department of Pharmacology, University of Life Sciences, Lublin, Poland.
authors.forename: Cezary J
authors.initials: CJ
authors.lastname: Kowaski
authors.affiliation: Department of Veterinary Sciences, University of Pisa, San Piero a Grado, Italy.
authors.forename: Mario
authors.identifier: http://orcid.org/0000-0003-3657-4703
authors.initials: M
authors.lastname: Giorgi
mesh_terms: D000284:Administration, Oral; D000285:Administration, Rectal; D000631:Aminopyridines / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D000818:Animals; D003692:Delayed-Action Preparations; D004285:Dogs; D005260:Female; D007275:Injections, Intravenous / Q000662:veterinary; D008297:Male
chemical_list: D000631:Aminopyridines; D018712:Analgesics, Non-Narcotic; D003692:Delayed-Action Preparations; C034161:flupirtine
keywords: analgesic; biopharmaceutics; dogs; flupirtine; pharmacokinetics