• Yu-Qing Gao, Harald Ihmsen, Zhi-Yan Hu, Wei Sun, Yu-Bo Fang, Zhen Wang, Jürgen Schüttler, Christian Jeleazcov, and Hua-Cheng Liu.
• Department of Anesthesiology and Perioperative Medicine, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China; Key Laboratory of Pediatric Anesthesiology, Ministry of Education, Wenzhou Medical University, Wenzhou, Zhejiang, China; Key Laboratory of Anesthesiology of Zhejiang Province, Wenzhou Medical University, Wenzhou, Zhejiang, China.
• Br J Anaesth. 2023 Nov 1; 131 (5): 914920914-920.

BackgroundThe pharmacokinetic properties of the new benzodiazepine remimazolam have been studied only in adults. We investigated the pharmacokinetics of remimazolam after i.v. infusion in anaesthetised paediatric patients.MethodsTwenty-four children (2-6 yr, ASA physical status 1-2, BMI 15-18 kg m-2) undergoing general anaesthesia with sevoflurane were enrolled. During surgery, remimazolam was administered as an i.v. infusion over 1 h at 5 mg kg-1 h-1 for 5 min, followed by 1.5 mg kg-1 h-1 for 55 min. Plasma concentrations of remimazolam and its metabolite CNS7054 were determined from arterial blood samples using ultra-high performance liquid chromatography-mass spectrometry. Pharmacokinetic modelling was performed by population analysis.ResultsPharmacokinetics were best described by a three-compartment model for remimazolam and a two-compartment model for CNS7054 linked by a transit compartment. Remimazolam showed a high clearance of 15.9 (12.9, 18.2) ml kg-1 min-1 (median, Q25, Q75), a small central volume of distribution of 0.11 (0.08, 0.14) L kg-1 and a short terminal half-life of 67 (49, 85) min. The context-sensitive half-time after an infusion of 4 h was 17 (12, 21) min. The metabolite CNS7054 showed a low clearance of 0.89 (0.33, 1.40) ml kg-1 min-1, a small central volume of distribution of 0.011 (0.005, 0.016) L kg-1, and a long terminal half-life of 321 (230, 770) min.ConclusionsRemimazolam in children was characterised by a high clearance and short context-sensitive half-time. When normalised to weight, pharmacokinetic properties were similar to those reported for adults.Clinical Trial RegistrationChiCTR2200057629.Copyright © 2023 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.

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