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Plasma pharmacokinetics of alfaxalone after a single intraperitoneal or intravenous injection of Alfaxan ® in rats
Author(s) -
Lau C.,
Ranasinghe M. G.,
Shiels I.,
Keates H.,
Pasloske K.,
Bellingham M. C.
Publication year - 2013
Publication title -
journal of veterinary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.527
H-Index - 60
eISSN - 1365-2885
pISSN - 0140-7783
DOI - 10.1111/jvp.12055
Subject(s) - dosing , pharmacokinetics , bioavailability , pharmacology , anesthesia , pharmacodynamics , premedication , medicine , chemistry
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 t 1/2elim 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. Cl p 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 C max 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. AUC 0–60 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 t 1/2elim and Cl p 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.