TY - JOUR
T1 - Pharmacokinetics of alfaxalone infusions, context-sensitive half-time and recovery times in male neutered cats
AU - Pypendop, Bruno H
AU - Ranasinghe, M. G.
AU - Pasloske, Kirby
PY - 2018/1/1
Y1 - 2018/1/1
N2 - 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.
AB - 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.
KW - alfaxalone
KW - cats
KW - pharmacology
KW - population pharmacokinetics
KW - target-controlled infusion
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U2 - 10.1016/j.vaa.2018.06.003
DO - 10.1016/j.vaa.2018.06.003
M3 - Article
C2 - 30057008
AN - SCOPUS:85050403173
JO - Veterinary Anaesthesia and Analgesia
JF - Veterinary Anaesthesia and Analgesia
SN - 1467-2987
ER -