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.
Department of Anesthesiology, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Erlangen, Germany.
Br J Anaesth. 2023 Nov;131(5):914-920. doi: 10.1016/j.bja.2023.08.019. Epub 2023 Sep 21.
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.
Twenty-four children (2-6 yr, ASA physical status 1-2, BMI 15-18 kg m) undergoing general anaesthesia with sevoflurane were enrolled. During surgery, remimazolam was administered as an i.v. infusion over 1 h at 5 mg kg h for 5 min, followed by 1.5 mg kg h 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.
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 min (median, Q, Q), a small central volume of distribution of 0.11 (0.08, 0.14) L kg 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 min, a small central volume of distribution of 0.011 (0.005, 0.016) L kg, and a long terminal half-life of 321 (230, 770) min.
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.
ChiCTR2200057629.
新苯二氮䓬类药物雷米唑仑的药代动力学特性仅在成人中进行了研究。我们研究了麻醉小儿患者静脉输注雷米唑仑后的药代动力学。
24 名年龄在 2-6 岁、ASA 身体状况 1-2 级、BMI 为 15-18kgm 的小儿接受七氟醚全身麻醉。手术期间，雷米唑仑以 5mgkg h 的速度静脉输注 1 小时，输注 5 分钟后以 1.5mgkg h 的速度输注 55 分钟。使用超高效液相色谱-质谱法从动脉血样中测定雷米唑仑及其代谢物 CNS7054 的血浆浓度。通过群体分析进行药代动力学建模。
雷米唑仑的药代动力学最好用三室模型描述，CNS7054 用两室模型描述，通过转运室连接。雷米唑仑表现出高清除率 15.9（12.9，18.2）mlkg min（中位数，Q，Q），小中央分布容积 0.11（0.08，0.14）Lkg 和短终末半衰期 67（49，85）min。输注 4 小时后的上下文敏感半衰期为 17（12，21）min。代谢物 CNS7054 表现出低清除率 0.89（0.33，1.40）mlkg min，小中央分布容积 0.011（0.005，0.016）Lkg，长终末半衰期 321（230，770）min。
儿童雷米唑仑的特点是清除率高，上下文敏感半衰期短。当按体重归一化时，药代动力学特性与成人报道的相似。
ChiCTR2200057629。
