Pharmacokinetics of alfaxalone infusions, context-sensitive half-time and recovery times in male neutered cats

Abstract

Objectives: To determine the context-sensitive half-time of alfaxalone following intravenous infusions of various durations. To estimate the time necessary for plasma concentration to decrease by up to 95%.

Study design: Prospective randomized and simulation studies.

Animals: A group of six 1-year-old male castrated research cats.

Methods: Cats were instrumented with catheters in a jugular and a medial saphenous vein. Alfaxalone was administered using a target-controlled infusion system, to target a plasma alfaxalone concentration of 7.6 mg L^-1. The infusion lasted 30 (n = 2), 60 (n = 2) or 240 (n = 2) minutes. Blood samples were collected prior to drug administration, and at several times during and up to 8 hours after the infusion, for the determination of plasma alfaxalone concentration using liquid chromatography/tandem mass spectrometry. Compartment models were fitted to each time-concentration profile, and a population model was fitted to data from all individuals. The context-sensitive half-time was determined from each individual model. In addition, times for plasma alfaxalone concentration to decrease by 50-95% following bolus administration and target-controlled infusions or continuous rate infusions of 0.5-8 hours were estimated by simulation using the population model.

Results: Context-sensitive half-times were 2 and 8, 6 and 9, and 18 and 20 minutes for the 30, 60 and 240 minutes, respectively. Time for plasma alfaxalone concentration to decrease by 90% was predicted to range from 7 to 120 or 113 minutes following a bolus to an 8 hour target-controlled or continuous rate infusion, respectively.

Conclusion and clinical relevance: Recovery time from alfaxalone anesthesia in cats is predicted to be influenced by the duration of target-controlled infusion.

Keywords: alfaxalone; cats; pharmacology; population pharmacokinetics; target-controlled infusion.