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Population Pharmacokinetics of Intranasal Dexmedetomidine in Infants and Young Children

Li, Bi L; Guan, Yan P; Yuen, Vivian M; Wei, Wei; Huang, Min; Zhang, Ma Z; Li, Ai W; ... Song, Xing R; + view all (2022) Population Pharmacokinetics of Intranasal Dexmedetomidine in Infants and Young Children. Anesthesiology , 137 (2) pp. 163-175. 10.1097/ALN.0000000000004258. Green open access

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Abstract

Background: 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. Methods: Intranasal dexmedetomidine 2 µg · kg-1was 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. Results: 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-1within 20 min, and the average peak concentration of 0.563 ng · ml-1could be attained at 61 min. Conclusions: 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-1could achieve a preset therapeutic threshold of mild to moderate sedation that lasted for up to 2 h.

Type: Article
Title: Population Pharmacokinetics of Intranasal Dexmedetomidine in Infants and Young Children
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1097/ALN.0000000000004258
Publisher version: https://doi.org/10.1097/ALN.0000000000004258
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Science & Technology, Life Sciences & Biomedicine, Anesthesiology, HANDLING DATA, QUANTIFICATION, PREMEDICATION, CLEARANCE, SEDATION, LIMIT
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Infection, Immunity and Inflammation Dept
URI: https://discovery.ucl.ac.uk/id/eprint/10160280
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