Vancomycin is a synthetic antibiotic effective against Gram-positive pathogens. Although the clinical applicability of vancomycin for infants has been increasing, the pharmacokinetic data for vancomycin in extremely low-birth-weight infants are limited. The aim of this study was to construct a population pharmacokinetics model for vancomycin in extremely-low-birth-weight infants and establish an optimal dosage regimen. We enrolled children aged less than 1 year with a birth weight of less than 1,000 g and body weight at vancomycin prescription of less than 1,500 g. Pharmacokinetic data from 19 patients were analyzed, and a population pharmacokinetics model was developed using nonlinear mixed-effects modeling software. Goodness-of-fit plots, a nonparametric bootstrap analysis, and a prediction-corrected visual predictive check were employed to evaluate the final model. The dosage regimen was optimized based on the final model. The pharmacokinetic data fit a one-compartment model with first-order elimination, and body weight and estimated serum creatinine level were used as significant covariates. In a simulation using the final model, the optimal dosage regimen, especially when the serum creatinine level (>0.6 mg/dl) was high, was 5.0 to 7.5 mg/kg of body weight twice a day every 12 h; this was required to reduce the dosage compared with that in previous studies. The recommended doses based on the current target time course concentration curves may not be appropriate for extremely-low-birth-weight infants.

中文翻译：

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日本极低出生体重婴儿的群体药代动力学分析和剂量方案优化

万古霉素是一种合成抗生素，对革兰氏阳性病原体有效。尽管万古霉素对婴儿的临床适用性不断提高，但万古霉素在极低出生体重儿中的药代动力学数据有限。本研究的目的是构建万古霉素在极低出生体重儿中的群体药代动力学模型并建立最佳给药方案。我们招募了出生体重小于 1,000 g 且万古霉素处方体重小于 1,500 g 的 1 岁以下儿童。分析了 19 名患者的药代动力学数据，并使用非线性混合效应建模软件开发了群体药代动力学模型。拟合优度图，非参数自举分析，并采用预测校正的视觉预测检查来评估最终模型。基于最终模型优化给药方案。药代动力学数据符合一级消除的单室模型，体重和估计的血清肌酐水平被用作重要的协变量。在使用最终模型的模拟中，最佳剂量方案，尤其是当血清肌酐水平 (>0.6 mg/dl) 较高时，为 5.0 至 7.5 mg/kg 体重，每天两次，每 12 小时一次；与以前的研究相比，这是减少剂量所必需的。基于当前目标时间过程浓度曲线的推荐剂量可能不适用于极低出生体重婴儿。药代动力学数据符合一级消除的单室模型，体重和估计的血清肌酐水平被用作重要的协变量。在使用最终模型的模拟中，最佳剂量方案，尤其是当血清肌酐水平 (>0.6 mg/dl) 较高时，为 5.0 至 7.5 mg/kg 体重，每天两次，每 12 小时一次；与以前的研究相比，这是减少剂量所必需的。基于当前目标时间过程浓度曲线的推荐剂量可能不适用于极低出生体重婴儿。药代动力学数据符合一级消除的单室模型，体重和估计的血清肌酐水平被用作重要的协变量。在使用最终模型的模拟中，最佳剂量方案，尤其是当血清肌酐水平 (>0.6 mg/dl) 较高时，为 5.0 至 7.5 mg/kg 体重，每天两次，每 12 小时一次；与以前的研究相比，这是减少剂量所必需的。基于当前目标时间过程浓度曲线的推荐剂量可能不适用于极低出生体重婴儿。6 mg/dl) 高，每 12 小时每天两次 5.0 至 7.5 mg/kg 体重；与以前的研究相比，这是减少剂量所必需的。基于当前目标时间过程浓度曲线的推荐剂量可能不适用于极低出生体重婴儿。6 mg/dl) 高，每 12 小时每天两次 5.0 至 7.5 mg/kg 体重；与以前的研究相比，这是减少剂量所必需的。基于当前目标时间过程浓度曲线的推荐剂量可能不适用于极低出生体重婴儿。