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

Goodwin, Wendy; Keates, H.; Pasloske, Kirby; Pearson, M. R B; Sauer, B.; Ranasinghe, M. G.

doi:10.1111/j.1467-2995.2012.00734.x

Cited by 32 publications

(33 citation statements)

References 26 publications

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“…Goodwin et al . reported respiratory depression and hypoxaemia in neonatal foals premedicated with butorphanol and anaesthetised with alfaxalone . Additionally Pearson et al .…”

Section: Discussionmentioning

confidence: 96%

Alfaxalone and medetomidine intravenous infusion to maintain anaesthesia in colts undergoing field castration

Goodwin

Keates

Pearson

et al. 2012

Equine Veterinary Journal

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“…Goodwin et al . reported respiratory depression and hypoxaemia in neonatal foals premedicated with butorphanol and anaesthetised with alfaxalone . Additionally Pearson et al .…”

Section: Discussionmentioning

confidence: 96%

Alfaxalone and medetomidine intravenous infusion to maintain anaesthesia in colts undergoing field castration

Goodwin

Keates

Pearson

et al. 2012

Equine Veterinary Journal

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“…The mean Cl p in rats following i.v. injection was similar to that reported for the dog [53 and 59 mL/kg/min for 2 and 10 mg/ kg ], but was larger than the mean Cl p reported for cats, horses and foals with 25, 37 and 20 mL/ min/kg, for 5, 1 and 3 mg/kg i.v., respectively, Goodwin et al, 2011Goodwin et al, , 2012. In contrast to the high Cl p of alfaxalone following i.v.…”

Section: Rodent Anaesthesia Surveymentioning

confidence: 95%

“…, cats , horses and pigs Goodwin et al, 2011Goodwin et al, , 2012, with a fivefold margin of safety at supraclinical doses in dogs and cats . The pharmacokinetic parameters of alfaxalone have been defined in cats (single/multiple doses), dogs (single dose) and horses (single dose) Goodwin et al, 2011Goodwin et al, , 2012.…”

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confidence: 99%

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The safety, efficacy and neuromotor effects of the neurosteroid anaesthetic alfaxalone in rats

Lau¹

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Rodents are routinely anaesthetised for husbandry and biomedical research purposes. All anaesthetics carry a degree of risk, complications and side effects. An ideal anaesthetic for rodents is safe, predictable, alleviates pain and distress and can be performed without specialist training. A survey was created to identify anaesthetic agents frequently administered to rodents currently utilised by the research community. Findings indicated injectable anaesthetics were very commonly used and complications were often associated with use, highlighting the lack of a safe, predictable laboratory rodent anaesthetic protocol.Alfaxalone is a neuroactive steroid injectable anaesthetic agent with a high margin of safety, and is commonly used in veterinary anaesthesia as the Alfaxan® formulation. I sought to establish whether alfaxalone could be used as an injectable anaesthetic agent for laboratory rodents. A plasma pharmacokinetics study was performed using IV and IP Alfaxan® in adult female Wistar rats (7-10 weeks). Mean T 1/2elim for 2 and 5 mg.kg -1 IV was short (~17 minutes), but could not be estimated for IP dosing due to sustained plasma levels for up to 60 minutes after injection. Cl p for IV injection was calculated at 24.5% and 23% of cardiac output respectively. The observed C max was 2.99 mg.L -1 for IP administration, and 2.2 ± 0.9 and 5.2 ± 1.3 mg.L -1 for 2 and 5 mg.kg -1 IV administration respectively. AUC 0-60 was 96 min.mg.L -1 for IP dosing. The relative bioavailability for IP dosing was 26% and 28%, compared to IV doses of 2 and 5mg.kg -1 respectively. Alfaxalone given IP caused longer sleep times than IV dosing, although anaesthesia was not induced in 30% of rats.Importantly, all rats exhibited muscle twitching after alfaxalone administration. I then sought to test whether combining IP injection of Alfaxalone with common premedication agents could improve anaesthetic induction rates and reduce muscle twitching, to provide a viable anaesthetic regimen for rats. Medetomidine (0.5 mg.kg -1 ), medetomidine-butorphanol (0.35 mg.kg -1 -0.2 mg.kg -1 ), Acetylpromazine (ACP) -methadone (3 mg.kg -1 -0.7 mg.kg -1 ) and ACP-xylazine (3 mg.kg -1 -3 mg.kg -1 )were administered IP 10 minutes prior to IP alfaxalone (20 mg.kg -1 ). ACP-xylazine, medetomidine and medetomidine-butorphanol all significantly reduced twitching. Medetomidine-butorphanol provided surgical anaesthesia without prolonged recovery and provided an adequate plane of anaesthesia for short painful surgical procedures.However, none of these premedication agents fully eliminated alfaxalone-induced muscle twitching. I therefore carried out electrophysiological studies of motor neurons (MN), to determine the mechanism causing neuromotor excitation in response to alfaxalone. Previous data has shown that alfaxalone can modulate strychnine-sensitive glycinergic receptors, which may, in part, contribute to the adverse neuromotor excitatory responses manifested as muscle twitching during alfaxalone anaesthesia. The 3 effects of alfaxalone on inhibito...

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“…Several experimental trials of alfaxalone in horses have been reported [14–18]. It is reported that the effects of alfaxalone in relation to induction of anesthesia, recovery quality, and cardiopulmonary response in Thoroughbred horses are similar to the effects of ketamine and thiopental [18], and that alfaxalone has a number of pharmacological properties which are desirable for CRI in horses [14, 19]. It is also reported that the co-administration of alfaxalone and medetomidine as CRI after induction of anesthesia with alfaxalone is suitable for short-term anesthesia in horses undergoing field castration [20].…”

Section: Introductionmentioning

confidence: 99%

Clinical evaluation of constant rate infusion of alfaxalone–medetomidine combined with sevoflurane anesthesia in Thoroughbred racehorses undergoing arthroscopic surgery

et al. 2018

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BackgroundAlfaxalone has a number of pharmacological properties which are desirable for constant rate infusion (CRI). Previously, the co-administration of alfaxalone and medetomidine is shown to be suitable for short-term anesthesia in horses. However, the use of alfaxalone–medetomidine CRI with inhalational anesthesia under surgical procedures have not been investigated in clinical cases. The aim of the present study was to evaluate the clinical efficacy of alfaxalone–medetomidine CRI in sevoflurane-anesthetized Thoroughbred racehorses undergoing arthroscopic surgery. Sevoflurane requirement, cardiovascular function, and induction/recovery quality were compared between horses maintained with sevoflurane in combination with medetomidine CRI (3 µg/kg/h) (Group M; n = 25) and those maintained with sevoflurane in combination with alfaxalone–medetomidine CRI (0.5 mg/kg/h and 3 µg/kg/h, respectively) (Group AM; n = 25).ResultsThe mean end-tidal sevoflurane concentrations were significantly lower in Group AM (1.8 ± 0.2%) than in Group M (2.4 ± 0.1%). The mean dobutamine infusion rate required for maintaining mean arterial blood pressure within the target values (60–80 mmHg) was significantly lower in Group AM (0.53 ± 0.20 µg/kg/min) than in Group M (0.85 ± 0.32 µg/kg/min). Induction and recovery scores were not significantly different between two groups. However, excitatory response during recovery were observed in five horses in Group AM. The mean plasma alfaxalone concentrations were stable throughout the maintenance period (0.77 ± 0.12 to 0.85 ± 0.13 µg/mL), and decreased significantly immediately after standing (0.32 ± 0.07 µg/mL).ConclusionsAlfaxalone–medetomidine CRI reduced sevoflurane requirement by approximately 26% with good maintenance of cardiopulmonary function in Thoroughbred racehorses undergoing arthroscopic surgery. Sevoflurane in combination with alfaxalone–medetomidine CRI may be a clinically effective anesthetic technique for Thoroughbred racehorses. However, 20% of horses administered alfaxalone showed remarkable excitatory response during recovery. Greater attention to excitatory response may be advisable if alfaxalone is used for induction or maintenance of anesthesia. A larger study is needed to explore the clinical relevance of these findings.

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

Cited by 32 publications

References 26 publications

Alfaxalone and medetomidine intravenous infusion to maintain anaesthesia in colts undergoing field castration

Alfaxalone and medetomidine intravenous infusion to maintain anaesthesia in colts undergoing field castration

The safety, efficacy and neuromotor effects of the neurosteroid anaesthetic alfaxalone in rats

Clinical evaluation of constant rate infusion of alfaxalone–medetomidine combined with sevoflurane anesthesia in Thoroughbred racehorses undergoing arthroscopic surgery

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