Department of Small Animal Clinical Sciences, School of Veterinary Medicine, Rakuno Gakuen University, Ebetsu, Hokkaido 069-8591, Japan.
Research Regulatory Management Department, Drug Discovery Research, Astellas Pharma Inc., Tsukuba, Ibaraki 305-8585, Japan.
J Vet Med Sci. 2020 Jul 31;82(7):1021-1029. doi: 10.1292/jvms.20-0043. Epub 2020 May 26.
To evaluate the sedative and physiological effects of alfaxalone intramuscular (IM) administration, 12 healthy cynomolgus monkeys were administered single IM doses of alfaxalone at 0.625 mg/kg (ALFX0.625), 1.25 mg/kg (ALFX1.25), 2.5 mg/kg (ALFX2.5), 5 mg/kg (ALFX5), 7.5 mg/kg (ALFX7.5), or 10 mg/kg (ALFX10); saline was used as the control (CONT). The sedative effects were subjectively evaluated using a composite measure scoring system in six animals. Changes in respiratory rate, pulse rate, non-invasive blood pressure, percutaneous oxygen-hemoglobin saturation (SpO), and rectal temperature were observed after IM treatments in the other six animals. All animals were allowed to lay down following the ALFX5, ALFX7.5, and ALFX10 treatments, whereas lateral recumbency was achieved in only two animals after ALFX2.5 treatment and none after the CONT, ALFX 0.625, and ALFX1.25 treatments. The median time (interquartile range) to lateral recumbency was 6.5 min (5.3-7.8), 4.0 min (4.0-4.0), and 3.0 min (3.0-3.8), and the duration of immobilization was 27.5 min (19.0-33.8), 56.0 min (42.3-60.8), and 74.5 min (62.8-78.0) after the ALFX5, ALFX7.5, and ALFX10 treatments, respectively. Endotracheal intubation was achieved in all six animals after the ALFX7.5 and ALFX10 treatments. Dose-dependent decreases in respiratory rate, non-invasive blood pressure, SpO, and rectal temperature were observed, and the quality of recovery was smooth in all animals after the ALFX5, ALFX7.5, and ALFX10 treatments. Thus, alfaxalone IM induced a dose-dependent sedative effect in cynomolgus monkeys, but at higher doses, hypotension, hypoxemia, and hypothermia could be induced.
为了评估肌肉内给予氟马西尼的镇静和生理效应，将 12 只健康的食蟹猴给予单剂量 0.625mg/kg（ALFX0.625）、1.25mg/kg（ALFX1.25）、2.5mg/kg（ALFX2.5）、5mg/kg（ALFX5）、7.5mg/kg（ALFX7.5）或 10mg/kg（ALFX10）的氟马西尼肌内注射；生理盐水作为对照（CONT）。在 6 只动物中，使用综合评分系统主观评估镇静作用。在其他 6 只动物中，在肌内治疗后观察呼吸频率、脉搏率、无创血压、经皮血氧饱和度（SpO）和直肠温度的变化。在给予 ALFX5、ALFX7.5 和 ALFX10 治疗后，所有动物都允许躺下，而在给予 ALFX2.5 治疗后只有 2 只动物侧卧，在给予 CONT、ALFX0.625 和 ALFX1.25 治疗后没有动物侧卧。侧卧的中位时间（四分位间距）为 6.5min（5.3-7.8）、4.0min（4.0-4.0）和 3.0min（3.0-3.8），并且在给予 ALFX5、ALFX7.5 和 ALFX10 后，动物的固定时间分别为 27.5min（19.0-33.8）、56.0min（42.3-60.8）和 74.5min（62.8-78.0）。在给予 ALFX7.5 和 ALFX10 后，所有 6 只动物均进行了气管内插管。观察到呼吸频率、无创血压、SpO 和直肠温度的剂量依赖性降低，并且在给予 ALFX5、ALFX7.5 和 ALFX10 后，所有动物的恢复质量均平稳。因此，氟马西尼肌内注射在食蟹猴中引起了剂量依赖性的镇静作用，但在较高剂量下可能会引起低血压、低氧血症和低体温。
