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

Autor: Millagahamanda G Ranasinghe, Hervé P. Lefebvre, Qiang Li, Kirby Pasloske, Ted Whittem, Pierre J Ferré
Přispěvatelé: Inconnu
Rok vydání: 2006
Předmět:
Zdroj: Veterinary Anaesthesia and Analgesia
Veterinary Anaesthesia and Analgesia, Wiley, 2006, 33 (4), pp.229-236. ⟨10.1111/j.1467-2995.2005.00264.x⟩
ISSN: 1467-2987
1467-2995
DOI: 10.1111/j.1467-2995.2005.00264.x⟩
Popis: 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). Experimental design 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 and Clinical relevance 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.
Databáze: OpenAIRE
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