title: Plasma pharmacokinetics of alfaxalone in dogs after an intravenous bolus of Alfaxan-CD RTU.
abstract: OBJECTIVE
  To determine the pharmacokinetic parameters of alfaxalone in dogs after the intravenous (IV) administration of clinical and supra-clinical doses of a 2-hydroxypropyl-beta-cyclodextrin (HPCD) alfaxalone formulation (Alfaxan-CD RTU).
  
  
  METHODS
  Prospective two-period crossover design. Animals Eight (four male and four female) young adult healthy Beagle dogs. Methods The steroid anaesthetic alfaxalone was administered IV at two doses in a crossover design (2 and 10 mg kg(-1)) with a washout period of 21 days. Blood samples were collected before and up to 8 hours after dosing. Plasma concentrations of alfaxalone were assayed using a liquid chromatograph/mass selective detector technique and analyzed to estimate the main pharmacokinetic parameters by noncompartmental analysis. Results were expressed as mean +/- SD.
  
  
  RESULTS
  The mean duration of anaesthesia from endotracheal intubation to extubation was 6.4 +/- 2.9 and 26.2 +/- 7.5 minutes, for the 2 and 10 mg kg(-1) doses, respectively. The plasma clearance of alfaxalone for the 2 and 10 mg kg(-1) doses differed statistically at 59.4 +/- 12.9 and 52.9 +/- 12.8 mL kg(-1) minute(-1), respectively (p = 0.008) but this difference was deemed clinically unimportant; the harmonic mean plasma terminal half-lives (t(1/2)) were 24.0 +/- 1.9 and 37.4 +/- 1.6 minutes respectively. The volume of distribution was between 2 and 3 L kg(-1) and did not differ between the two doses. No sex effect was observed.
  
  
  CONCLUSIONS
  Alfaxalone, as an HPCD formulation (Alfaxan-CD RTU) administered in the dog provides rapid and smooth induction of anaesthesia, satisfactory conditions for endotracheal intubation and a short duration of anaesthesia. There was no clinically significant modification of the pharmacokinetic parameters between sexes and between the clinical (2 mg kg(-1)) and supra-clinical (10 mg kg(-1)) doses.
authors.affiliation: UMR 181 Physiopathologie et Toxicologie Expérimentales INRA-ENVT, France.
authors.forename: Pierre J
authors.initials: PJ
authors.lastname: Ferré
authors.forename: Kirby
authors.initials: K
authors.lastname: Pasloske
authors.forename: Ted
authors.initials: T
authors.lastname: Whittem
authors.forename: Millagahamanda G
authors.initials: MG
authors.lastname: Ranasinghe
authors.forename: Qiang
authors.initials: Q
authors.lastname: Li
authors.forename: Hervé P
authors.initials: HP
authors.lastname: Lefebvre
mesh_terms: D000768:Anesthesia, General / Q000662:veterinary*; D000777:Anesthetics / Q000097:blood / Q000493:pharmacokinetics*; D000818:Animals; D019540:Area Under Curve; D002626:Chemistry, Pharmaceutical; D018592:Cross-Over Studies; D004285:Dogs / Q000378:metabolism* / Q000502:physiology* / Q000601:surgery; D005260:Female; D007275:Injections, Intravenous / Q000662:veterinary; D008297:Male; D011277:Pregnanediones / Q000097:blood / Q000493:pharmacokinetics*; D011446:Prospective Studies
chemical_list: D000777:Anesthetics; D011277:Pregnanediones; C006477:alphaxalone