Department of Clinical Pharmacy, College of Pharmacy, King Saud University, P. O. Box 2457, Riyadh, 11451, Saudi Arabia.
Pediatric Clinical Pharmacy Services, King Saud University Medical City, King Saud University, Riyadh, Saudi Arabia.
Paediatr Drugs. 2018 Jun;20(3):265-272. doi: 10.1007/s40272-018-0288-y.
Our objective was to determine the population pharmacokinetic parameters of amikacin in pediatric patients to contribute to the future development of a revised optimum dose and population-specific dosing regimens.
We performed a retrospective chart review in non-critical pediatric patients (aged 1-12 years) who received amikacin for suspected or proven Gram-negative infection at a university hospital. The population pharmacokinetic models were developed using Monolix 4.4. Pharmacokinetic/pharmacodynamic (PK/PD) simulations were performed to explore the ability of different dosage regimens to achieve the pharmacodynamic targets.
The analysis included 134 amikacin plasma concentrations from 67 patients with a mean ± standard deviation age of 4.1 ± 3.9 years and bodyweight of 15 ± 8.4 kg. The patients received an amikacin total daily dose (TDD) of 23 ± 7.3 mg/kg, which resulted in peak and trough concentrations of 20.65 ± 7.6 and 2.4 ± 1.7 mg/l, respectively. The estimated pharmacokinetic parameters for amikacin were 1.2 l/h and 6.5 l for total body clearance (CL) and the volume of distribution (V), respectively. Dosing simulations showed that the standard dosing regimen (15 mg/kg/day) of amikacin achieved the PK/PD target of peak serum concentration (C)/minimum inhibitory concentration (MIC) ≥ 8 for an MIC of 2 mg/l; higher doses were required to achieve higher MIC values.
The simulation results indicated that amikacin 20 mg/kg once daily provided a higher probability of target attainment with lower toxicity than dosing three times daily. In addition, combination therapy is recommended for pathogens with an MIC of ≥ 8 mg/l.
本研究旨在确定儿童患者中阿米卡星的群体药代动力学参数，为未来制定优化剂量和人群特异性给药方案提供参考。
我们对一家大学医院收治的疑似或确诊革兰氏阴性感染的非危重症儿科患者（年龄 1-12 岁）进行了回顾性图表审查，并使用 Monolix 4.4 建立群体药代动力学模型。进行药代动力学/药效学（PK/PD）模拟，以探索不同给药方案实现药效学目标的能力。
分析纳入了 67 例患者的 134 份阿米卡星血药浓度，这些患者的平均（±标准差）年龄为 4.1±3.9 岁，体重为 15±8.4kg。患者接受的阿米卡星总日剂量（TDD）为 23±7.3mg/kg，导致峰浓度和谷浓度分别为 20.65±7.6mg/l 和 2.4±1.7mg/l。阿米卡星的估计药代动力学参数为 1.2l/h 和 6.5l，分别为总体清除率（CL）和分布容积（V）。给药模拟结果表明，阿米卡星标准剂量方案（15mg/kg/天）可实现 MIC 为 2mg/l 时的 PK/PD 目标，即峰血清浓度（C）/最低抑菌浓度（MIC）≥8；需要更高的剂量才能达到更高的 MIC 值。
模拟结果表明，与每日三次给药相比，每日一次给予 20mg/kg 的阿米卡星可提高目标达标率，同时降低毒性。此外，对于 MIC≥8mg/l 的病原体，建议联合治疗。
