Tan Lu, Chao Ailing, Liang Heng, Liu Qian, Han Minzhen, Guan Yanping
Department of Pharmacy, The Third Affiliated Hospital of Southern Medical University, Guangzhou, Guangdong, China.
Institute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, Guangdong, China.
Per Med. 2025 Jun;22(3):141-149. doi: 10.1080/17410541.2025.2499442. Epub 2025 Apr 30.
Vancomycin dosing in neonates is challenging due to developmental pharmacokinetic variability. The study was to characterize vancomycin pharmacokinetics in a large cohort of preterm and term neonates and develop individualized dosing regimens.
MATERIALS & METHODS: A 5-year retrospective study of a cohort of 255 neonates was included.
An allometric one-compartment model with first-order elimination best described the vancomycin concentrations. The population pharmacokinetic estimates (between subject variability) of clearance (CL) and volume of distribution (V) were 2.58 L·h·70 kg (9.00 %) and 52.09 L·70 kg (29.00%), respectively. CL and V were significantly influenced by body weight and postmenstrual age. Vancomycin CL reached 50% of adult values at 43.6 weeks PMA (a sigmoid Emax model). Renal maturation, estimated by creatinine production rate, was a significant covariate. Bayesian-guided individualized dosage regimens were developed and evaluated.
Vancomycin overdosage should be avoided in very young premature babies (PMA = 25 weeks). Optimization of efficacy while minimizing toxicity of vancomycin in preterm and term neonates is needed, especially guided by personalized body weight, postmenstrual age, and renal function.
由于发育过程中的药代动力学变异性，新生儿万古霉素给药具有挑战性。本研究旨在描述一大群早产儿和足月儿的万古霉素药代动力学特征，并制定个体化给药方案。
纳入一项对255例新生儿队列进行的为期5年的回顾性研究。
具有一级消除的异速一室模型最能描述万古霉素浓度。清除率（CL）和分布容积（V）的群体药代动力学估计值（个体间变异性）分别为2.58 L·h·70 kg（9.00%）和52.09 L·70 kg（29.00%）。CL和V受体重和孕龄的显著影响。在孕龄43.6周时，万古霉素CL达到成人值的50%（S型Emax模型）。以肌酐生成率估算的肾脏成熟度是一个显著的协变量。制定并评估了贝叶斯指导的个体化给药方案。
应避免在极年幼的早产儿（孕龄=25周）中出现万古霉素过量。需要在优化疗效的同时，尽量降低早产儿和足月儿万古霉素的毒性，尤其是要根据个体体重、孕龄和肾功能进行指导。
