Plasma pharmacokinetics of alfaxalone after a single intraperitoneal or intravenous injection of Alfaxan((R)) in rats

Lau, C., Ranasinghe, M. G., Shiels, I., Keates, H., Pasloske, K. and Bellingham, M. C. (2013) Plasma pharmacokinetics of alfaxalone after a single intraperitoneal or intravenous injection of Alfaxan((R)) in rats. Journal of Veterinary Pharmacology and Therapeutics, 36 5: 516-520. doi:10.1111/jvp.12055


Author Lau, C.
Ranasinghe, M. G.
Shiels, I.
Keates, H.
Pasloske, K.
Bellingham, M. C.
Title Plasma pharmacokinetics of alfaxalone after a single intraperitoneal or intravenous injection of Alfaxan((R)) in rats
Journal name Journal of Veterinary Pharmacology and Therapeutics   Check publisher's open access policy
ISSN 0140-7783
1365-2885
Publication date 2013-10
Sub-type Article (original research)
DOI 10.1111/jvp.12055
Volume 36
Issue 5
Start page 516
End page 520
Total pages 5
Place of publication Chichester, West Sussex, United Kingdom
Publisher Wiley-Blackwell
Collection year 2014
Language eng
Formatted abstract
Alfaxalone (3α-hydroxy-5α-pregnane-11, 20-dione) is a neuroactive steroid with anaesthetic properties and a wide margin of safety. The pharmacokinetic properties of alfaxalone administered intravenously and intraperitoneally in rats (n = 28) were investigated. Mean t1/2elim for 2 and 5 mg/kg i.v. was 16.2 and 17.6 min, respectively, but could not be estimated for IP dosing, due to sustained plasma levels for up to 60 min after injection. Clp for i.v. injection was calculated at 57.8 ± 23.6 and 54.3 ± 6.8 mL/min/kg, which were 24.5% and 23% of cardiac output, respectively. The observed Cmax was 3.0 mg/L for IP administration, and 2.2 ± 0.9 and 5.2 ± 1.3 mg/L for 2 and 5 mg/kg i.v. administration, respectively. AUC0-60 was 96.2 min·mg/L for IP dosing. The relative bioavailability for IP dosing was 26% and 28% compared to i.v. dosing. Differences in t1/2elim and Clp from previous pharmacokinetic studies in rats are likely due to variations in alfaxalone formulation rather than sex differences. Alfaxan® given IP caused sustained levels of alfaxalone, no apnoea and longer sleep times than i.v. dosing, although immobilization was not induced in 30% of rats given Alfaxan® IP. A pharmacodynamic study of the effects of combining IP injection of Alfaxan® with other premedication agents is worthwhile, to determine whether improved anaesthesia induction could ultimately provide an alternative anaesthetic regimen for rats.
Keyword Alphaxalone
Pharmacodynamics
Metabolism
Anesthesia
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
School of Biomedical Sciences Publications
School of Veterinary Science Publications
 
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