首页|Population Pharmacokinetics of Intranasal Dexmedetomidine in Infants and Young Children

Population Pharmacokinetics of Intranasal Dexmedetomidine in Infants and Young Children

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  • NSTL
  • Lippincott Williams & Wilkins
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.

Ai W.,Li、Joseph F.,Standing、Guo P.,Zhong、Ma Z.,Zhang、Xing R.,Song、Bi L.,Li、Yan P.,Guan、Vivian M.,Yuen、Wei,Wei、Min,Huang

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Department of Pharmacology and Pharmacy, University of Hong Kong, Hong Kong, China.

Great Ormond Street Institute of Child Health, University College London, London, United Kingdom.

Institute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun Yat-Sen University

Department of Anesthesiology, Shanghai Children’s Medical Center, Shanghai Jiao Tong University

Department of Anesthesiology, Guangzhou Women and Children’s Medical Center, Guangzhou Medical

Department of Anesthesiology and Perioperative Medicine, Hong Kong Children’s Hospital, Hong Kong

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2022

10.1097/ALN.0000000000004258

Anesthesiology

Anesthesiology

SCI
ISSN：0003-3022
年,卷(期)：2022.137(2)
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