Yamada Takaaki, Emoto Chie, Fukuda Tsuyoshi, Motomura Yoshitomo, Inoue Hirosuke, Ohga Shouichi, Ieiri Ichiro
Department of Pharmacy, Kyushu University Hospital, Fukuoka, Japan.
Laboratory of Drug Metabolism and Pharmacokinetics, Showa Pharmaceutical University.
Ther Drug Monit. 2022 Jun 1;44(3):404-413. doi: 10.1097/FTD.0000000000000930.
Teicoplanin is a glycopeptide antibiotic used for the treatment of methicillin-resistant Staphylococcus aureus infections. To ensure successful target attainment, therapeutic drug monitoring-informed dosage adjustment is recommended. However, it relies on the experience of the clinician and the frequency of drug measurements. This study aimed to design a new optimal dosing regimen of teicoplanin with a maintenance dosing strategy for neonates and children based on their physiological characteristics.
Data from teicoplanin-treated patients (n = 214) were collected from electronic medical records. Covariate analyses were performed using population pharmacokinetic (PK) modeling with 399 serum teicoplanin concentrations from 48 neonates and 166 children. Multiple PK simulations were conducted to explore optimal dosing regimens that would allow control of the trough concentration to the target of 15-30 mg/L quicker than the current standard regimen.
Allometrically scaled body weight, postmenstrual age (PMA), renal function, and serum albumin were implemented as substantial covariates for teicoplanin clearance in a two-compartment PK model. Covariate analyses and comprehensive simulation assessments recommended the following modifications to the current regimen: (1) decreased dose for premature babies (PMA ≤28 weeks), (2) decreased dose for children with renal dysfunction, and (3) increased dose for children (0.5-11 years) with an estimated glomerular filtration rate of ≥90 mL/min/1.73 m2.
This study leverages real-world clinical information and proposes new optimal dosing regimens for teicoplanin in neonates and children through PK modeling and simulation analyses, taking into account the age, including PMA, and renal function of patients.
替考拉宁是一种用于治疗耐甲氧西林金黄色葡萄球菌感染的糖肽类抗生素。为确保治疗目标的实现，建议进行治疗药物监测指导下的剂量调整。然而，这依赖于临床医生的经验和药物测量的频率。本研究旨在根据新生儿和儿童的生理特征，设计一种新的替考拉宁最佳给药方案及维持给药策略。
从电子病历中收集接受替考拉宁治疗患者（n = 214）的数据。使用群体药代动力学（PK）模型对48例新生儿和166例儿童的399个血清替考拉宁浓度进行协变量分析。进行多次PK模拟，以探索能比当前标准方案更快地将谷浓度控制在15 - 30 mg/L目标范围内的最佳给药方案。
在二室PK模型中，将按体表面积法标化的体重、孕龄（PMA）、肾功能和血清白蛋白作为替考拉宁清除率的重要协变量。协变量分析和综合模拟评估建议对当前方案进行以下修改：（1）降低早产儿（PMA≤28周）的剂量；（2）降低肾功能不全儿童的剂量；（3）提高估计肾小球滤过率≥90 mL/min/1.73 m²的儿童（0.5 - 11岁）的剂量。
本研究利用真实世界的临床信息，通过PK建模和模拟分析，考虑患者的年龄（包括PMA）和肾功能，为新生儿和儿童提出了新的替考拉宁最佳给药方案。
