Pharmacokinetics of remimazolam after intravenous infusion in anaesthetised children

Gao YQ, Ihmsen H, Hu ZY, Sun W, Fang YB, Wang Z, Schüttler J, Jeleazcov C, Liu HC (2023)

Publication Type: Journal article

Publication year: 2023

Journal

British Journal of Anaesthesia Oxford University Press (OUP): Policy B - Oxford Open Option B

DOI: 10.1016/j.bja.2023.08.019

Abstract

Background: The 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. Methods: Twenty-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. Results: Pharmacokinetics 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. Conclusions: Remimazolam 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 registration: ChiCTR2200057629.

Authors with CRIS profile

Harald Ihmsen Department of Anaesthesiology Jürgen Schüttler Lehrstuhl für Anästhesiologie Christian Jeleazcov Medizinische Fakultät

Involved external institutions

Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University / 温州医科大学附属第二医院 CN China (CN) Hangzhou First People's Hospital / Nanjing Medical University affiliated Hangzhou hospital / 杭州市第一人民医院 CN China (CN)

How to cite

APA:

Gao, Y.Q., Ihmsen, H., Hu, Z.Y., Sun, W., Fang, Y.B., Wang, Z.,... Liu, H.C. (2023). Pharmacokinetics of remimazolam after intravenous infusion in anaesthetised children. British Journal of Anaesthesia. https://dx.doi.org/10.1016/j.bja.2023.08.019

MLA:

Gao, Yu Qing, et al. "Pharmacokinetics of remimazolam after intravenous infusion in anaesthetised children." British Journal of Anaesthesia (2023).

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