Validation of a pediatric population pharmacokinetic model for vancomycin.
Validation of a pediatric population pharmacokinetic model for vancomycin.
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DOI：
10.1097/ftd.0000000000000153
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发表时间：
2015-06
影响因子：
2.5
通讯作者：
Vinks AA
中科院分区：
文献类型：
--
作者：
Hahn A;Frenck RW Jr;Zou Y;Vinks AA
万古霉素通常用于治疗儿童严重感染，包括耐甲氧西林金黄色葡萄球菌（MRSA）感染。预测万古霉素治疗成人MRSA感染效果的最佳药效学指标是最小抑制浓度（AUC/MIC）曲线下24小时的面积。虽然已经发表了多种儿童万古霉素群体药代动力学（PK）模型，但很少使用贝叶斯优化。目前的护理标准仍然是测量万古霉素血清谷浓度作为AUC的替代标志物。对万古霉素的儿童人群PK模型进行了前瞻性验证。在辛辛那提儿童医院医疗中心（CCHMC）接受万古霉素治疗的住院儿童< 18岁被邀请参与。使用峰值、谷值和随机万古霉素血清浓度对个体PK参数进行贝叶斯估计。模型协变量包括年龄、体重和血清肌酐。为了评估模型的预测性能，测量精度和偏差，并使用95%置信区间进行比较。纳入15名受试者；13名受试者按方案绘制万古霉素血清浓度。在这13名受试者中，年龄中位数为6岁，54%为男性。重要的医疗条件包括癌症（54%）、肺病（23%）、神经系统疾病（23%）和既往移植（15%）。初始血清肌酐正常（中位数0.33,IQR 0.23-0.4 mg/dL），无潜在肾功能障碍。发现原始模型验证与CCHMC验证的偏差和精度相等。使用贝叶斯估计的万古霉素儿童人群PK模型可以可靠地预测儿童万古霉素暴露。单独使用AUC代替谷血药浓度可以最大限度地优化儿童万古霉素给药。
Vancomycin is often required to treat serious infections in children, including methicillin resistant Staphylococcus aureus (MRSA) infections. The pharmacodynamic index that best predicts efficacy with vancomycin use for MRSA infection in adults is the 24 hour area under the curve over the minimum inhibitory concentration (AUC/MIC). While multiple pediatric population pharmacokinetic (PK) vancomycin models have been published, few use Bayesian optimization. The current standard of care remains measuring vancomycin serum trough concentrations as a surrogate marker of AUC. A prospective validation of a pediatric population PK model of vancomycin was performed. Hospitalized children < 18 years of age receiving vancomycin at Cincinnati Children's Hospital Medical Center (CCHMC) were invited to participate. Peak, trough, and random vancomycin serum concentrations were used for Bayesian estimation of individual PK parameters. Model covariates included age, weight, and serum creatinine. To evaluate the predictive performance of the model, precision and bias were measured and compared using the 95% confidence interval. 15 subjects were enrolled; 13 subjects had vancomycin serum concentrations drawn per protocol. Of those 13 subjects, the median age was 6 years and 54% were male. Significant medical conditions included cancer (54%), lung disease (23%), neurologic disorders (23%), and prior transplantation (15%). The initial serum creatinine was normal (median 0.33, IQR 0.23-0.4 mg/dL), and none had underlying renal dysfunction. Equivalence of bias and precision between the original model validation and the CCHMC validation were found. Pediatric population PK models for vancomycin with Bayesian estimation can be used to reliably predict vancomycin exposure in children. Using AUC instead of trough serum concentrations alone can provide an opportunity to maximally optimize vancomycin administration in children.