Sedative and physiological effects of alfaxalone intramuscular administration in cynomolgus monkeys (<i>Macaca fascicularis</i>)

Abstract

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 2 ), 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 2 , 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.

Development, refinement, and characterization of a nonhuman primate critical care environment

“…Our group switched to this combination for the final two NHPs. Short-term NHP studies have shown that at low to moderate doses, alfaxalone preserves heart rate and mean arterial pressure, while producing effective sedation and analgesia [30][31][32]. Alfaxalone does appear to reduce cerebral blood flow and contribute to hypothermia, with higher doses also exerting suppressive cardiovascular effects [30][31][32].…”

The use of alfaxalone for short-term anesthesia can confound serum progesterone measurements in the common marmoset: a case report

“…It shows certain benefits compared to other anesthetic agents due to a broad margin of safety and a low cumulative effect after repeated doses, which enables a rapid recovery (Lau et al, 2013;Ferre et al, 2006;Rezende, 2015). Alfaxalone is used for both induction and maintenance of anesthesia in many species including companion and experimental animal species such as dog (White and Yates, 2017), cat (Khenissi et al, 2017), goat (Abouelfetouh et al, 2021), sheep (Andaluz et al, 2012), pig (Bigby et al, 2017), horse (Goodwin et al, 2011), rhesus macaque (Bertrand et al, 2017), cynomolgus monkey (Casoni et al, 2015), and common marmoset (Bakker et al, 2013). Alfaxalone anesthesia has minimal negative impact on the cardiorespiratory system though it can cause hypoxemia if administrated in high doses (Wada et al, 2020).…”

“…Alfaxalone is used for both induction and maintenance of anesthesia in many species including companion and experimental animal species such as dog (White and Yates, 2017), cat (Khenissi et al, 2017), goat (Abouelfetouh et al, 2021), sheep (Andaluz et al, 2012), pig (Bigby et al, 2017), horse (Goodwin et al, 2011), rhesus macaque (Bertrand et al, 2017), cynomolgus monkey (Casoni et al, 2015), and common marmoset (Bakker et al, 2013). Alfaxalone anesthesia has minimal negative impact on the cardiorespiratory system though it can cause hypoxemia if administrated in high doses (Wada et al, 2020). It is also commonly used without side effects in pregnant dogs showing no negative effects on the stability of maternal and fetal hemodynamics (Andaluz et al, 2013;Metcalfe et al, 2014).…”