Li Bi L, Guan Yan P, Yuen Vivian M, Wei Wei, Huang Min, Zhang Ma Z, Li Ai W, Standing Joseph F, Zhong Guo P, Song Xing R
Department of Anesthesiology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.
Institute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, China.
Anesthesiology. 2022 Aug 1;137(2):163-175. doi: 10.1097/ALN.0000000000004258.
Intranasal dexmedetomidine provides noninvasive, effective procedural sedation for pediatric patients, and has been widely used in clinical practice. However, the dosage applied has varied fourfold in pediatric clinical studies. To validate an appropriate dosing regimen, this study investigated the pharmacokinetics of intranasal dexmedetomidine in Chinese children under 3 yr old.
Intranasal dexmedetomidine 2 µg · kg-1 was administered to children with simple vascular malformations undergoing interventional radiological procedures. A population pharmacokinetic analysis with data from an optimized sparse-sampling design was performed using nonlinear mixed-effects modeling. Clearance was modeled using allometric scaling and a sigmoid postmenstrual age maturation model. Monte Carlo simulations were performed to assess the different dosing regimens.
A total of 586 samples from 137 children aged 3 to 36 months were included in the trial. The data were adequately described by a two-compartment model with first-order elimination. Body weight with allometric scaling and maturation function were significant covariates of dexmedetomidine clearance. The pharmacokinetic parameters for the median subjects (weight 10 kg and postmenstrual age 101 weeks) in the authors' study were apparent central volume of distribution 7.55 l, apparent clearance of central compartment 9.92 l · h-1, apparent peripheral volume of distribution 7.80 l, and apparent intercompartmental clearance 61.7 l · h-1. The simulation indicated that at the dose of 2 µg · kg-1, 95% of simulated individuals could achieve a target therapeutic concentration of 0.3 ng · ml-1 within 20 min, and the average peak concentration of 0.563 ng · ml-1 could be attained at 61 min.
The pharmacokinetic characteristics of intranasal dexmedetomidine were evaluated in Chinese pediatric patients aged between 3 and 36 months. An evidence-based dosing regimen at 2 µg · kg-1 could achieve a preset therapeutic threshold of mild to moderate sedation that lasted for up to 2 h.
鼻内给予右美托咪定可为儿科患者提供无创、有效的程序性镇静，已在临床实践中广泛应用。然而，儿科临床研究中应用的剂量相差四倍。为验证合适的给药方案，本研究调查了3岁以下中国儿童鼻内给予右美托咪定后的药代动力学。
对患有单纯血管畸形并接受介入放射学检查的儿童给予2 μg·kg-1的鼻内右美托咪定。使用非线性混合效应模型对来自优化稀疏采样设计的数据进行群体药代动力学分析。清除率采用异速生长标度法和S形月经后年龄成熟模型进行建模。进行蒙特卡洛模拟以评估不同的给药方案。
该试验共纳入了137名3至36个月大儿童的586份样本。数据用具有一级消除的二室模型进行了充分描述。采用异速生长标度法的体重和成熟功能是右美托咪定清除率的显著协变量。作者研究中中位受试者（体重10 kg，月经后年龄101周）的药代动力学参数为表观中央分布容积7.55 l，中央室表观清除率9.92 l·h-1，表观外周分布容积7.80 l，以及表观室间清除率61.7 l·h-1。模拟表明，在2 μg·kg-1的剂量下，95%的模拟个体可在20分钟内达到0.3 ng·ml-1的目标治疗浓度，在61分钟时可达到平均峰值浓度0.563 ng·ml-1。
对3至36个月大的中国儿科患者鼻内给予右美托咪定的药代动力学特征进行了评估。基于证据的2 μg·kg-1给药方案可达到预设的轻度至中度镇静治疗阈值，且可持续长达2小时。
