Plasma pharmacokinetics and pharmacodynamics of alfaxalone in neonatal foals after an intravenous bolus of alfaxalone following premedication with butorphanol tartrate.

The study investigates the pharmacokinetics and pharmacodynamics of the anesthetic alfaxalone in baby horses after being administered intravenously and follows it up with the medication butorphanol tartrate. Overall, the usage of alfaxalone resulted in predictable and consistent anesthesia, with little cardiovascular depression.

Objective of the Study

• The purpose of this study was to find out the pharmacokinetics (what a body does to a drug) and pharmacodynamics (what a drug does to the body) of alfaxalone, a neurosteroid anesthetic, in baby horses (neonatal foals) after a single intravenous injection of alfaxalone given after premedication with butorphanol tartrate, a pain reliever.

Methods

• Five clinically healthy Australian Stock Horse foals of average age 12 ± 3 days, weighing 67.3 ± 12.4 kg, were the subjects of this prospective experimental study.
• The foals were premedicated with butorphanol (0.05 mg kg(-1) IV) and put under anesthesia 10 minutes later with an IV injection of alfaxalone 3 mg kg(-1).
• Throughout the anesthesia, various heart and respiratory factors (pulse rate, respiratory rate, direct arterial blood pressure, arterial blood gases) and clinical signs of depth of anesthesia were evaluated.
• Venous blood samples were collected at strategic time points to determine alfaxalone plasma concentrations using liquid chromatography-mass spectrometry (LC/MS) and analysed by noncompartmental pharmacokinetic analysis.

Results

• The average plasma elimination half-life (t½) for alfaxalone was found to be 22.8 ± 5.2 minutes.
• The plasma clearance (the volume of plasma cleared of the drug per unit time) and volume of distribution were 19.9 ± 5.9 mL minute kg(-1) and 0.6 ± 0.2 L kg(-1) respectively.
• Overall, the inductions and recoveries of the anesthetic were good, and most monitored physiological variables were clinically acceptable in all foals, although some foals did experience a short period of low oxygen levels following recumbency.
• The average duration of the anesthesia from induction to first movement was 18.7 ± 7 minutes, while from induction to standing was 37.2 ± 4.7 minutes.

Conclusions

• The anesthesia protocol used in this study provided a predictable and consistent plane of anesthesia in the five foals studied, with minimal negative impact on the cardiovascular system.
• In foals as well as adult horses, alfaxalone has a short elimination half-life.
• Alfaxalone appears to be a suitable anesthetic induction agent in foals and the established pharmacokinetics suggest that with continuous infusion, it could provide prolonged anesthesia.
• For foals undergoing anesthesia, oxygen supplementation is recommended.