de Hoog M, Schoemaker R C, Mouton J W, van den Anker J N
Department of Pediatrics, Erasmus University and University Hospital Rotterdam/Sophia Children's Hospital, The Netherlands.
Clin Pharmacol Ther. 2000 Apr;67(4):360-7. doi: 10.1067/mcp.2000.105353.
Recently the value of vancomycin therapeutic drug monitoring, as well as the required therapeutic range, has been subject of debate, resulting in new recommendations. This study was performed to incorporate these new insights in an up-to-date dosing scheme for neonates of various gestational ages.
In this retrospective study with prospective validation, 108 newborns with suspected central line-related septicemia during the first month of life received 30 mg/kg/day vancomycin divided into two doses regardless of gestational or postconceptional age. Trough and peak vancomycin serum concentrations were determined before and after the third dose. Vancomycin data were analyzed according to a one-compartment open model with use of NONMEM population pharmacokinetic software. Model parameters were evaluated and then used to simulate vancomycin dosing for different dose and dose interval combinations. Targets were a trough concentration between 5 and 15 mg/L and a peak below 40 mg/L. In the prospective study, the optimal scheme was tested in 22 patients.
Of the 108 patients, 34.3% of measured trough concentrations and 17.6% of peak concentrations were outside the desired therapeutic range. The model that best fitted the data included clearance and volume per kilogram and was independent of gestational age. Simulation of various dosing schemes showed that a dosing schedule of 30 mg/kg/day, irrespective of gestational age, in three doses was optimal, and this scheme was prospectively tested. Mean trough concentrations before the second dose were 8.2 +/- 2.2 mg/L versus a predicted trough of 8.9 +/- 2.5 mg/L. No peak levels higher than 40 mg/L were found.
The use of the proposed schedule leads to adequate vancomycin trough serum concentrations, and there is no need for routine monitoring of peak serum concentrations.
最近，万古霉素治疗药物监测的价值以及所需的治疗范围一直存在争议，从而产生了新的建议。本研究旨在将这些新见解纳入针对不同胎龄新生儿的最新给药方案中。
在这项具有前瞻性验证的回顾性研究中，108例出生后第一个月内疑似中心静脉导管相关败血症的新生儿，无论其胎龄或孕龄如何，均接受30mg/kg/天的万古霉素，分两次给药。在第三次给药前后测定万古霉素血清谷浓度和峰浓度。使用NONMEM群体药代动力学软件，根据一室开放模型分析万古霉素数据。评估模型参数，然后用于模拟不同剂量和给药间隔组合的万古霉素给药。目标是谷浓度在5至15mg/L之间，峰浓度低于40mg/L。在前瞻性研究中，对22例患者测试了最佳方案。
108例患者中，34.3%的实测谷浓度和17.6%的峰浓度超出了预期的治疗范围。最符合数据的模型包括每千克体重的清除率和容积，且与胎龄无关。对各种给药方案的模拟表明，无论胎龄如何，30mg/kg/天分三次给药的方案是最佳的，并对该方案进行了前瞻性测试。第二次给药前的平均谷浓度为8.2±2.2mg/L，而预测谷浓度为8.9±2.5mg/L。未发现峰浓度高于40mg/L。
采用建议的给药方案可使万古霉素血清谷浓度达到合适水平，无需常规监测血清峰浓度。
