The pharmacokinetics and pharmacodynamics of the injectable anaesthetic alfaxalone in the horse

Abstract

ObjectiveTo 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. Study designProspective experimental study. AnimalsTen (five male and five female), adult, healthy, Standardbred horses. MethodsHorses 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). ResultsThe 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 (t1/2), plasma clearance (Clp) and volume of distribution (Vd) 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 and clinical relevanceAlfaxalone, 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.