Plasma pharmacokinetics of alfaxalone in dogs after an intravenous bolus of Alfaxan-CD RTU

Abstract

ObjectiveTo 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). Experimental designProspective two-period crossover design. AnimalsEight (four male and four female) young adult healthy Beagle dogs. MethodsThe 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. ResultsThe 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 (t1/2) 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 and Clinical relevanceAlfaxalone, 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.