Clinical pharmacokinetics and pharmacodynamics of intravenous alfaxalone in young Thoroughbred horses premedicated with medetomidine and midazolam

To investigate the clinical pharmacokinetics and pharmacodynamics of intravenous alfaxalone in young Thoroughbred horses, seven Thoroughbred horses were randomly anaesthetised twice with either 1 or 2 mg/kg of intravenous alfaxalone after premedication with medetomidine (6 µg/kg intravenous) and midazolam (20 µg/kg intravenous). Blood samples were collected at predetermined time points up to two hours after administration. Plasma alfaxalone concentrations were quantified by a liquid chromatography tandem-mass spectrometry method and analysed by non-compartmental pharmacokinetic analysis. Induction and recovery qualities were good to excellent for both doses. Recovery time for the 2 mg/kg (median 90 minutes) was significantly longer than that for the 1 mg/kg (median 50 minutes). Respiratory rate for the 2 mg/kg was significantly lower than that for the 1 mg/kg, resulting in hypoxaemia. The median (range) elimination half-life, total clearance and volume of distribution were 58.2 (42.3–70.7) minutes, 11.6 (10.3–14.5) ml/minute/kg and 0.8 (0.7–0.9) l/kg for the 1 mg/kg and 59.8 (47.5–68.0) minutes, 14.7 (12.1–16.0) ml/minute/kg and 0.9 (0.9–1.2) l/kg for the 2 mg/kg, respectively. Alfaxalone is rapidly eliminated from the plasma in young Thoroughbred horses. Respiratory depression should be especially noted when alfaxalone is used in clinical practice.