title: The pharmacokinetics and pharmacodynamics of the injectable anaesthetic alfaxalone in the horse.
abstract: OBJECTIVE
  To determine the pharmacokinetics and pharmacodynamics of the neurosteroidal anaesthetic, alfaxalone, in horses after a single intravenous (IV) injection of alfaxalone, following premedication with acepromazine, xylazine and guaiphenesin.
  
  
  METHODS
  Prospective experimental study.
  
  
  METHODS
  Ten (five male and five female), adult, healthy, Standardbred horses.
  
  
  METHODS
  Horses were premedicated with acepromazine (0.03 mg kg(-1) IV). Twenty minutes later they received xylazine (1 mg kg(-1) IV), then after 5 minutes, guaiphenesin (35 mg kg(-1) IV) followed immediately by IV induction of anaesthesia with alfaxalone (1 mg kg(-1) ). Cardiorespiratory variables (pulse rate, respiratory rate, pulse oximetry) and clinical signs of anaesthetic depth were evaluated throughout anaesthesia. Venous blood samples were collected at strategic time points and plasma concentrations of alfaxalone were assayed using liquid chromatography-mass spectrometry (LC/MS) and analysed by noncompartmental pharmacokinetic analysis. The quality of anaesthetic induction and recovery was scored on a scale of 1-5 (1 very poor, 5 excellent).
  
  
  RESULTS
  The median (range) induction and recovery scores were 4 (3-5) (good: horse slowly and moderately gently attained recumbency with minimal or no rigidity or paddling) and 4 (1-5) (good: horse stood on first attempt with some knuckling and ataxia) respectively. The monitored cardiopulmonary variables were within the range expected for clinical equine anaesthesia. The mean ± SD durations of anaesthesia from induction to sternal recumbency and from induction to standing were 42.7 ± 8.4 and 47 ± 9.6 minutes, respectively. The mean ± SD plasma elimination half life (t(1/2) ), plasma clearance (Clp) and volume of distribution (V(d) ) for alfaxalone were 33.4 minutes, 37.1 ± 11.1 mL minute(-1)  kg(-1) and 1.6 ± 0.4 L kg(-1) , respectively.
  
  
  CONCLUSIONS
  Alfaxalone, in a 2-hydroxypropyl-beta-cyclodextrin formulation, provides anaesthesia with a short duration of recumbency that is characterised by a smooth induction and satisfactory recovery in the horse. As in other species, alfaxalone is rapidly cleared from the plasma in the horse.
authors.affiliation: School of Veterinary Science, University of Queensland, Brisbane, Qld, Australia. w.goodwin@uq.edu.au
authors.forename: Wendy A
authors.initials: WA
authors.lastname: Goodwin
authors.forename: Helen L
authors.initials: HL
authors.lastname: Keates
authors.forename: Kirby
authors.initials: K
authors.lastname: Pasloske
authors.forename: Martin
authors.initials: M
authors.lastname: Pearson
authors.forename: Ben
authors.initials: B
authors.lastname: Sauer
authors.forename: Millaganamada Gedara
authors.initials: MG
authors.lastname: Ranasinghe
mesh_terms: D000771:Anesthesia, Intravenous / Q000379:methods / Q000662:veterinary; D018686:Anesthetics, Intravenous / Q000493:pharmacokinetics* / Q000494:pharmacology; D000818:Animals; D005260:Female; D006140:Guaifenesin; D006339:Heart Rate / Q000187:drug effects; D006454:Hemoglobins / Q000032:analysis; D006736:Horses; D006993:Hypnotics and Sedatives; D007275:Injections, Intravenous / Q000662:veterinary; D008297:Male; D011277:Pregnanediones / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D056152:Respiratory Rate / Q000187:drug effects; D014991:Xylazine
chemical_list: D018686:Anesthetics, Intravenous; D006454:Hemoglobins; D006993:Hypnotics and Sedatives; D011277:Pregnanediones; D014991:Xylazine; D006140:Guaifenesin; C006477:alphaxalone