可生物吸收,皮下纳尔特雷克森植入物减轻芬太尼诱导的呼吸抑制3个月-一项针对雄性犬的试点研究
Robert L Joyner1, Joseph A Hollenbaugh2, Donald D'Aquila1
1Richard A. Henson Research Institute, TidalHealth Peninsula Regional Salisbury, Salisbury, Maryland, USA.
Physiological reports
|August 9, 2024
概括
延长释放的纳尔特雷克松 (NTX) 植入物有效地减少了芬太尼引起的狗的呼吸抑制. 这项研究表明,BIOPIN植入物有潜力减轻人类阿片类药物过量服用的影响.
科学领域:
- 药理学 药理学是指药理学的学科.
- 生物材料科学 生物材料科学
- 兽医医学 兽医医学 兽医医学
背景情况:
- 芬太尼过量服用是一个重大的公共卫生危机,往往导致致命的呼吸系统抑郁.
- 纳尔特雷是一种阿片类药物对抗剂,但其短暂的作用时间限制了其在治疗急性过量或长期阿片类药物暴露方面的有效性.
- 延长释放的纳尔特雷配方可以提供持续的对抗作用,为缓解阿片类药物诱导的呼吸抑制提供潜在的解决方案.
研究的目的:
- 评估延长释放,生物吸收,皮下纳尔特雷克森 (NTX) 植入物的有效性,以减轻静脉注射芬太尼产生的呼吸抑制.
- 在狗模型中评估不同生物吸收多聚合物植入物纳特雷克松 (BIOPIN) 配方的安全性和有效性.
主要方法:
- 使用Poly-d,l-乳酸 (PDLLA) 和/或Polycaprolactone (PCL) 的六种BIOPIN配方被开发成皮下植入物.
- 男犬接受了安慰剂或NTX植入物 (644毫克或1288毫克).
- 在植入后97-100天,狗被挑战增加静脉注射剂量的芬太尼 (30-120μg/kg),以评估呼吸速率 (RR).
主要成果:
- 安慰剂组的狗在30μg/kg芬太尼剂量后显示RR减少了~50%.
- 带有BIOPIN NTX植入物的狗可以耐受高达60μg/kg的芬太尼剂量,没有显著的呼吸抑制 (<50%的RR减少).
- 在NTX植入的狗中,在使用更高剂量的芬太尼 (90和120微克/公斤) 时发生了严重的呼吸抑制,但与安慰剂组相比,它们表现出更好的耐受性.
结论:
- 可生物吸收,延长释放的BIOPIN纳尔特雷克松植入物在植入后大约3个月的狗中有效减轻芬太尼诱导的呼吸抑制.
- 从BIOPIN植入物中持续释放的纳尔特雷表明,这是一个有希望的治疗策略,用于管理急性芬太尼毒性.
- 这项技术有可能预防和治疗芬太尼引起的人类呼吸系统抑郁症,为阿片类药物过量管理提供一种新的方法.
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