Effective plasma alfaxalone concentration to produce immobility in male neutered cats

Abstract

Objective: To determine the effective plasma alfaxalone concentration for the production of immobility in cats.

Study design: Prospective up-and-down study.

Animals: Sixteen 1-2 year old male castrated research cats.

Methods: Cats were instrumented with catheters in a jugular and a medial saphenous vein. Alfaxalone was administered via the medial saphenous catheter, using a target-controlled infusion system. The infusion lasted for approximately 32 minutes. A noxious stimulus (tail clamp) was applied 30 minutes after starting the alfaxalone infusion, until the cat moved or 60 seconds had elapsed, whichever occurred first. The target alfaxalone concentration was set at 5 mg L^-1 in the first cat and increased or decreased by 1 mg L^-1 in subsequent cats, if the previous cat had moved or not moved in response to stimulation, respectively. This was continued until six independent crossovers (different responses in pairs of subsequent cats) had been observed. Blood samples were collected before alfaxalone administration, and 15 and 31 minutes after starting the administration, for the determination of plasma alfaxalone concentration using liquid chromatography/tandem mass spectrometry. The alfaxalone concentration yielding a probability of immobility in 50% (EC₅₀), 95% (EC₉₅) and 99% (EC₉₉) of the population, and their respective 95% Wald confidence intervals were calculated.

Results: The EC₅₀, EC₉₅ and EC₉₉ for alfaxalone-induced immobility were 3.7 (2.4-4.9), 6.2 (4.7-) and 7.6 (5.5-) mg L^-1, respectively.

Conclusions and clinical relevance: The effective plasma alfaxalone concentration for immobility in cats was determined. This value will help in the design of pharmacokinetic-based dosing regimens.

Keywords: alfaxalone; cats; pharmacology.