Pharmacokinetics and effects of alfaxalone after intravenous and intramuscular administration to cats

N Z Vet J. 2018 Jul;66(4):172-177. doi: 10.1080/00480169.2018.1455541. Epub 2018 Apr 2.

Abstract

Aims: To determine the pharmacokinetics, and anaesthetic and sedative effects of alfaxalone after I/V and I/M administration to cats.

Methods: Six European shorthair cats, three males and three females, with a mean weight of 4.21 (SD 0.53) kg and aged 3.8 (SD 0.9) years were enrolled in this crossover, two-treatment, two-period study. Alfaxalone at a dose of 5 mg/kg was administered either I/V or I/M. Blood samples were collected between 2-480 minutes after drug administration and analysed for concentrations of alfaxalone by HPLC. The plasma concentration-time curves were analysed by non-compartmental analysis. Sedation scores were evaluated between 5-120 minutes after drug administration using a numerical rating scale (from 0-18). Intervals from drug administration to sit, sternal and lateral recumbency during the induction phase, and to head-lift, sternal recumbency and standing position during recovery were recorded.

Results: The mean half-life and mean residence time of alfaxalone were longer after I/M (1.28 (SD 0.21) and 2.09 (SD 0.36) hours, respectively) than after I/V (0.49 (SD 0.07) and 0.66 (SD 0.16) hours, respectively) administration (p<0.05). Bioavailability after I/M injection of alfaxalone was 94.7 (SD 19.8)%. The mean intervals to sternal and lateral recumbency were longer in the I/M (3.73 (SD 1.99) and 6.12 (SD 0.90) minutes, respectively) compared to I/V (0 minutes for all animals) treated cats (p<0.01). Sedation scores indicative of general anaesthesia (scores >15) were recorded from 5-15 minutes after I/V administration and deep sedation (scores 11-15) at 20 and 30 minutes. Deep sedation was observed from 10-45 minutes after I/M administration. One cat from each group showed hyperkinesia during recovery, and the remainder had an uneventful recovery.

Conclusions and clinical relevance: Alfaxalone administered I/V in cats provides rapid and smooth induction of anaesthesia. After I/M administration, a longer exposure to the drug and an extended half life were obtained compared to I/V administration. Therefore I/M administration of alfaxalone could be a reliable, suitable and easy route in cats, taking into account that alfaxalone has a slower onset of sedation than when given I/V and achieves deep sedation rather than general anaesthesia.

Keywords: Pharmacokinetics; alfaxalone; anaesthesia; cats; intramuscular; sedation.

MeSH terms

  • Administration, Intravenous / veterinary
  • Analysis of Variance
  • Anesthesia Recovery Period
  • Anesthetics / administration & dosage
  • Anesthetics / blood
  • Anesthetics / pharmacokinetics*
  • Anesthetics / pharmacology
  • Anesthetics, Inhalation
  • Animals
  • Area Under Curve
  • Biological Availability
  • Cats / metabolism
  • Cats / physiology*
  • Chromatography, High Pressure Liquid / veterinary
  • Cross-Over Studies
  • Deep Sedation / veterinary
  • Female
  • Half-Life
  • Hyperkinesis / chemically induced
  • Hyperkinesis / veterinary
  • Injections, Intramuscular / veterinary
  • Male
  • Methyl Ethers
  • Pregnanediones / administration & dosage
  • Pregnanediones / blood
  • Pregnanediones / pharmacokinetics*
  • Pregnanediones / pharmacology
  • Prospective Studies
  • Reproducibility of Results
  • Sevoflurane
  • Time Factors

Substances

  • Anesthetics
  • Anesthetics, Inhalation
  • Methyl Ethers
  • Pregnanediones
  • Sevoflurane
  • alphaxalone