Pharmacokinetics and sedative effects of alfaxalone with or without dexmedetomidine in rabbits

• Published in: Research in veterinary science 2020-04, Vol.129, p.6-12
• Main Authors: Marín, Pedro, Belda, Eliseo, Laredo, Francisco G., Torres, Crhystian A., Hernandis, Verónica, Escudero, Elisa
• Format: Article
• Language: English
• Subjects: Alfaxalone; Anaesthesia; Anesthesia; Catheters; Dexmedetomidine; Drug dosages; Heart rate; High performance liquid chromatography; Intravenous administration; Laboratory animals; Liquid chromatography; Pain; Pharmacokinetics; Pharmacology; Position measurement; Rabbits; Respiratory rate; Studies; Veterinary medicine
• ISSN: 0034-5288; 1532-2661
• DOI: 10.1016/j.rvsc.2019.12.015

This study aimed to investigate the specific pharmacokinetic profile and effects of alfaxalone after intravenous (IV) and intramuscular (IM) administration to rabbits and evaluate the potential interaction with dexmedetomidine. The study design was a blinded, randomized crossover with a washout period of 2 weeks. Five New Zealand white rabbits were used. Each animal received single IV and IM injections of alfaxalone at a single dose of 5 mg/kg, and single IV and IM injections of alfaxalone (5 mg/kg) combined with dexmedetomidine (100 μg/kg) administered intramuscularly. Blood samples were collected at predetermined times and analysed by high-performance liquid chromatography. The plasma concentration-time curves were analysed by non-compartmental analysis. Sedation/anaesthesia scores were evaluated by a modified numerical rating scale. At pre-determined time points heart and respiratory rates were measured. Times to sternal recumbency and standing position during the recovery were recorded. Concentrations of alfaxalone alone were very similar (slighty smaller) to concentrations when alfaxalone was combined with dexmedetomidine, after both routes of administration. Dexmedetomidine enhanced and increase the duration of the sedative effects of alfaxalone. In conclusion, alfaxalone administered in rabbits provides rapid and smooth onset of sedation. After IV and IM injections of alfaxalone combined with dexmedetomidine, a longer MRT and a deeper and extended sedation have been obtained compared to alfaxalone alone. Consequently, alfaxalone alone or in combination with dexmedetomidine could be useful to achieve respectively moderate to deep sedation in rabbits. •Intramuscular bioavailabilities of alfaxalone were high.•Alfaxalone as a sole agent did not increase the heart rate. The inclusion of dexmedetomidine clearly decreased it.•Addition of dexmedetomidine enhanced and increase the duration of the sedative effects of alfaxalone.•Alfaxalone alone or combined with dexmedetomidine could achieve moderate or deep sedation in rabbits, respectively.