Sedative and cardiorespiratory effects of intranasal atomized alfaxalone in Japanese White rabbits

To investigate the sedative and cardiorespiratory effects of intranasal atomization (INA) of alfaxalone using a mucosal atomization device in Japanese White rabbits.

Randomized, prospective, crossover study.

A total of eight healthy female rabbits, weighing 3.6-4.3 kg and aged 12-24 months.

Each rabbit was randomly assigned to four INA treatments administered 7 days apart: Control treatment, 0.15 mL 0.9% saline in both nostrils; treatment INA0.3, 0.15 mL 4% alfaxalone in both nostrils; treatment INA0.6, 0.3 mL 4% alfaxalone in both nostrils; treatment INA0.9, 0.3 mL 4% alfaxalone in left, then right, then left nostril. Sedation was scored 0-13 using a composite measure scoring system for rabbits. Simultaneously, pulse rate (PR), respiratory rate (f_R), noninvasive mean arterial pressure (MAP), peripheral hemoglobin oxygen saturation (SpO₂) and arterial blood gases were measured until 120 minutes. The rabbits breathed room air during the experiment and were administered flow-by oxygen when hypoxemia (SpO₂ <90% or PaO₂ <60 mmHg; 8.0 kPa) developed. Data were analyzed using the Fisher's exact test and the Friedman test (p < 0.05).

No rabbit was sedated in treatments Control and INA0.3. All rabbits in treatment INA0.9 developed loss of righting reflex for 15 (10-20) minutes [median (25th-75th percentile)]. Sedation score significantly increased from 5 to 30 minutes in treatments INA0.6 and INA0.9 with maximum scores of 2 (1-4) and 9 (9-9), respectively. f_R decreased in an alfaxalone dose-dependent manner and one rabbit developed hypoxemia in treatment INA0.9. No significant changes were observed in PR and MAP.

INA alfaxalone resulted in dose-dependent sedation and respiratory depression in Japanese White rabbits to values considered not clinically relevant. Further investigation of INA alfaxalone in combination with other drugs is warranted.