Abstract
The steroid anesthetic, alfaxalone, is commercially available for veterinary use in a formulation containing Cremophor-EL® and alfadalone acetate. The allergic sensitivity of some species to this formulation limits its veterinary application and also led to withdrawal of the product for human use. The present studies evaluated alfaxalone formulated as an inclusion complex with a mixture of 2-hydroxypropyl-β-cyclodextrin (HPCD) isomers for anesthetic properties in rats and dogs. Aqueous solutions of alfaxalone-HPCD showed identical anesthetic profiles in rats compared to the commercial formulation. In contrast, the anesthetic response to alfaxalone-HPCD in dogs was not accompanied with massive histamine release and pronounced decrease in respiration and blood pressure seen after the commercial preparation. Anesthesia induction and recovery phases were rapid and uncomplicated after alfaxalone-HPCD. An anaphylactoid-like response did occur in dogs after the same dose of alfaxalone as the commercial preparation. The favorable anesthetic profile of alfaxalone formulated as an HPCD complex together with previous toxicology and stability studies suggest that the steroid may be successfully formulated for intravenous dosing with modified cyclodextrins.
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