Zhang Tao, Sun Dan, Shu Zuocheng, Duan Ziyun, Liu Yang, Du Qian, Zhang Ying, Dong Yuzhu, Wang Taotao, Hu Sasa, Cheng Hua, Dong Yalin
Department of Pharmacy, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
Department of Pharmacy, The Affiliated Children Hospital of Xi'an Jiaotong University, Xi'an, China.
Front Pharmacol. 2020 Dec 8;11:594562. doi: 10.3389/fphar.2020.594562. eCollection 2020.
The pharmacokinetics (PK) of teicoplanin differs in children compared with adults. Our aim was to determine the PK of teicoplanin in an Asian pediatric population and to optimize dosage regimens. This was a retrospective PK study and all the data were collected from hospitalized children. We developed a population PK model using sparse data, and Monte Carlo simulation was used to assess the ability of standard teicoplanin regimen and other different dosage regimens. The optimal dosing regimens were defined as achieving the target trough concentration ( ) of 10 mg/L and pharmacokinetic/pharmacodynamic (PK/PD, [AUC/MIC]) of 125 for moderate infection. For severe infection, the optimal dosing regimens were defined as achieving the target 15 mg/L and AUC/MIC of 345. 159 children were included and 1.5 samples/children on average were provided. Estimated clearance of teicoplanin was 0.694 L/h (0.784/L/h/70 kg) and volume of distribution was 1.39 L. Teicoplanin standard loading dose was adequate for moderate infection, while 13 mg/kg was needed for severer infection. With standard maintenance doses, both patients with moderate and severe infection failed to achieve the target . 12 and 16 mg/kg/day were required to achieve a ≥ 10 and 15 mg/L, respectively. However, standard maintenance dose was adequate to achieve AUC/MIC ≥ 125 for moderate infection, and 12 mg/kg/day was needed to achieve AUC/MIC ≥ 345 for severe infection. Lower weight and serum creatinine were associated with higher dose. Optimal doses based on the target were higher than that based on the PK/PD target. To achieve the and PK/PD targets simultaneously, a standard loading dose was adequate for moderate infection based on simulation, while dosing higher than standard doses were required in other situation. Further clinical studies with rich sampling from children is required to confirm our findings.
与成人相比，替考拉宁在儿童中的药代动力学（PK）有所不同。我们的目的是确定替考拉宁在亚洲儿科人群中的PK，并优化给药方案。这是一项回顾性PK研究，所有数据均来自住院儿童。我们使用稀疏数据建立了群体PK模型，并采用蒙特卡罗模拟来评估标准替考拉宁方案和其他不同给药方案的效果。对于中度感染，最佳给药方案定义为达到10mg/L的目标谷浓度（ ）和125的药代动力学/药效学（PK/PD，[AUC/MIC]）。对于严重感染，最佳给药方案定义为达到15mg/L的目标和345的AUC/MIC。纳入了159名儿童，平均每名儿童提供1.5份样本。替考拉宁的估计清除率为0.694L/h（0.784/L/h/70kg），分布容积为1.39L。替考拉宁标准负荷剂量对中度感染足够，而严重感染则需要13mg/kg。采用标准维持剂量时，中度和重度感染患者均未达到目标 。分别需要12和16mg/kg/天才能使 ≥10和15mg/L。然而，标准维持剂量足以使中度感染的AUC/MIC≥125，严重感染则需要12mg/kg/天才能使AUC/MIC≥345。体重较低和血清肌酐水平与较高剂量相关。基于目标 的最佳剂量高于基于PK/PD目标的剂量。为了同时达到 和PK/PD目标，根据模拟结果，标准负荷剂量对中度感染足够，而在其他情况下则需要高于标准剂量的给药。需要对儿童进行更丰富采样的进一步临床研究来证实我们的发现。
