Vanky E, Hellmundt L, Bondesson U, Eksborg S, Lundeberg S
Department of Anesthesia and Intensive Care, Visby Hospital, Visby, Sweden.
Department of Pediatric Anesthesia and Intensive Care, Astrid Lindgren Children's Hospital, Karolinska University Hospital, Stockholm, Sweden.
Acta Anaesthesiol Scand. 2017 Jul;61(6):636-640. doi: 10.1111/aas.12898. Epub 2017 Apr 25.
There is increasing interest in the use of intranasal naloxone to reverse adverse opioid effects during management of procedural pain in children and in adults after overdose. There are limited data on the pharmacokinetics of intranasal naloxone so in this study we aimed to detail the pharmacokinetic profile of the commercially marketed injectable solution of naloxone 0.4 mg/ml when administered as an intranasal spray.
Twenty healthy volunteers received naloxone as an intranasal spray at a dose of 10 μg/kg. Venous blood sampling was carried out for 90 min after administration to determine the time profile of the plasma concentrations of using tandem mass spectrometry. Pharmacokinetic parameters were calculated using a one-compartment model.
Median time to maximum naloxone concentration (Tmax) was 14.5 (95% CI: 9.0-16.5) min, mean maximum naloxone concentration (Cmax) was 1.09 ± 0.56 ng/ml and mean AUC was 37.1 ± 15.0 ng*min/ml. Elimination half-life estimated from the median concentration data was 28.2 min.
Our results show a faster uptake of intranasal naloxone to maximum concentration compared with previous studies although with a marked variation in maximum concentration. The findings are consistent with our clinical experience of the time profile for reversing the effects of sufentanil sedation in children.
在儿童程序性疼痛管理及成人过量用药后，使用鼻内纳洛酮逆转阿片类药物不良反应的关注度日益增加。关于鼻内纳洛酮的药代动力学数据有限，因此在本研究中，我们旨在详细描述市售的0.4毫克/毫升纳洛酮注射溶液作为鼻喷雾剂给药时的药代动力学特征。
20名健康志愿者接受剂量为10微克/千克的鼻内纳洛酮喷雾剂。给药后90分钟进行静脉血采样，使用串联质谱法测定血浆浓度的时间变化情况。使用单室模型计算药代动力学参数。
纳洛酮浓度达到最大值的中位时间（Tmax）为14.5（95%置信区间：9.0 - 16.5）分钟，平均最大纳洛酮浓度（Cmax）为1.09±0.56纳克/毫升，平均曲线下面积（AUC）为37.1±15.0纳克·分钟/毫升。根据中位浓度数据估算的消除半衰期为28.2分钟。
我们的结果表明，与先前研究相比，鼻内纳洛酮达到最大浓度的吸收速度更快，尽管最大浓度存在显著差异。这些发现与我们在儿童中逆转舒芬太尼镇静作用的时间变化情况的临床经验一致。
