Vashisht Rita, Bendon Anju A, Okonkwo Ijeoma, Patel Davandra, Fullwood Catherine, Ogungbenro Kayode, Aarons Leon, Darwich Adam S
Department of Paediatric Anaesthesia, Manchester University NHS Foundation Trust, Royal Manchester Children's Hospital, Manchester, UK.
Biostatistics, Research and Innovation, Manchester University NHS Foundation Trust, The University of Manchester, Manchester, UK.
Paediatr Anaesth. 2019 Feb;29(2):161-168. doi: 10.1111/pan.13548. Epub 2018 Dec 19.
The local anesthetic, levobupivacaine, is the safer enantiomer of racemic bupivacaine. Present protocols for levobupivacaine are based on studies and pharmacokinetic modeling with racemic bupivacaine.
The aim is to investigate total serum levobupivacaine concentrations after a caudalepidural loading dose followed by a maintenance infusion over 48 hours in infants aged 3-6 months.
The clinical trial was conducted in eight infants aged 3-6 months, undergoing bladder exstrophy repair. Pharmacokinetic modeling allowed optimization of clinical sampling to measure total levobupivacaine and α -acid glycoprotein and prediction of the effect of α -acid glycoprotein on levobupivacaine plasma protein binding.
The observed median total levobupivacaine serum concentration was 0.30 mg/L (range: 0.20-0.70 mg/L) at 1 hour after the loading dose of 2 mg/kg. The median total levobupivacaine concentration after 47 hours of infusion, at 0.2 mg/kg/h, was 1.21 mg/L (0.07-1.85 mg/L). Concentrations of α -acid glycoprotein were found to rise throughout the study period. Pharmacokinetic modeling suggested that unbound levobupivacaine quickly reached steady state at a concentration of approximately 0.03 mg/L.
The study allows the development of a pharmacokinetic model, combining levobupivacaine and α -acid glycoprotein data. Modeling indicates that unbound levobupivacaine quickly reaches steady state once the infusion is started. Simulations suggest that it may be possible to continue the infusion beyond 48 hours.
局部麻醉药左旋布比卡因是消旋布比卡因的更安全对映体。目前左旋布比卡因的用药方案是基于对消旋布比卡因的研究和药代动力学模型制定的。
本研究旨在调查3至6个月大婴儿在单次骶管硬膜外负荷剂量给药后，持续48小时维持输注左旋布比卡因后的血清总浓度。
本临床试验纳入了8名年龄在3至6个月、正在接受膀胱外翻修复手术的婴儿。药代动力学模型可优化临床采样，以测量左旋布比卡因总量和α-酸性糖蛋白，并预测α-酸性糖蛋白对左旋布比卡因血浆蛋白结合的影响。
在给予2mg/kg负荷剂量后1小时，观察到的左旋布比卡因血清总浓度中位数为0.30mg/L（范围：0.20 - 0.70mg/L）。在以0.2mg/kg/h的速度输注47小时后，左旋布比卡因总浓度中位数为1.21mg/L（0.07 - 1.85mg/L）。研究期间发现α-酸性糖蛋白浓度持续上升。药代动力学模型表明，游离左旋布比卡因在浓度约为0.03mg/L时迅速达到稳态。
本研究建立了一个结合左旋布比卡因和α-酸性糖蛋白数据的药代动力学模型。模型显示，输注开始后游离左旋布比卡因迅速达到稳态。模拟结果表明，输注时间可能可以超过48小时。
