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

Abstract

ObjectiveTo investigate the sedative and cardiorespiratory effects of intranasal atomization (INA) of alfaxalone using a mucosal atomization device in Japanese White rabbits. Study designRandomized, prospective, crossover study. AnimalsA total of eight healthy female rabbits, weighing 3.6–4.3 kg and aged 12–24 months. MethodsEach 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 (fR), 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). ResultsNo 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. fR 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. Conclusions and clinical relevanceINA 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.