Beringer P M, Wong-Beringer A, Rho J P
Department of Clinical Pharmacy, School of Pharmacy, University of Southern California, Los Angeles 90033, USA.
Ann Pharmacother. 1998 Feb;32(2):176-81. doi: 10.1345/aph.17129.
To evaluate the Wragge-Cooper method of predicting vancomycin serum concentrations utilizing knowledge of aminoglycoside pharmacokinetic parameters in general medicine and intensive care unit populations, and to develop a revised model if necessary.
This study consists of two phases evaluating 50 adults receiving concurrent vancomycin and aminoglycoside therapy. Patients were identified by a retrospective review of medical records. Bayesian analysis of measured serum aminoglycoside and vancomycin concentrations was performed to determine the individualized pharmacokinetic parameters. Phase I of the study tested the predictive performance of a published model incorporating aminoglycoside elimination (Wragge-Cooper) in 25 patients (group 1), and a revised model was developed. Phase II determined the predictive performance of the revised model (revised) and its performance relative to the Wragge-Cooper model and a traditional model incorporating estimated creatinine clearance (traditional) in an additional 25 patients (group 2).
Two tertiary care university teaching hospitals.
The predictive performance of the models was determined by comparing predicted with measured vancomycin serum concentrations. Bias and precision were evaluated by calculating the mean prediction error (ME) and mean absolute error (MAE), respectively. Linear regression was performed to determine relationships between parameters.
The Wragge-Cooper model consistently underpredicts vancomycin serum concentrations in general medicine and intensive care unit populations (ME = -5.18, MAE = 6.63). Relative predictive performance analysis indicates no significant difference in bias or precision between the traditional and Wragge-Cooper models (delta ME 1.17, delta MAE -0.80). Regression analysis of individualized aminoglycoside and vancomycin elimination derived from patients in group 1 reveals the following relationship: vancomycin k10 (1/h) = 0.081 + 1.037ke,amg, r = 0.73. The revised model is significantly less biased and more precise compared with the traditional model (delta ME -4.48; delta MAE 1.22), and is significantly less biased (delta ME 4.29) but no more precise than the Wragge-Cooper model (delta MAE -0.58), using patients from group 2.
The revised model is an accurate method of predicting vancomycin serum concentrations in both general medicine and intensive care unit populations. Use of this model enables individualization of vancomycin dosage in patients receiving concurrent aminoglycoside therapy and minimizes vancomycin serum concentration monitoring.
利用普通内科和重症监护病房人群中氨基糖苷类药物的药代动力学参数知识，评估预测万古霉素血清浓度的Wragge-Cooper方法，并在必要时开发修订模型。
本研究包括两个阶段，对50名同时接受万古霉素和氨基糖苷类药物治疗的成年人进行评估。通过回顾病历识别患者。对测得的血清氨基糖苷类药物和万古霉素浓度进行贝叶斯分析，以确定个体化的药代动力学参数。研究的第一阶段在25名患者（第1组）中测试了一个纳入氨基糖苷类药物消除的已发表模型（Wragge-Cooper）的预测性能，并开发了一个修订模型。第二阶段在另外25名患者（第2组）中确定了修订模型（修订版）的预测性能及其相对于Wragge-Cooper模型和一个纳入估计肌酐清除率的传统模型（传统版）的性能。
两家三级大学教学医院。
通过比较预测的和测得的万古霉素血清浓度来确定模型的预测性能。分别通过计算平均预测误差（ME）和平均绝对误差（MAE）来评估偏差和精密度。进行线性回归以确定参数之间的关系。
Wragge-Cooper模型在普通内科和重症监护病房人群中始终低估万古霉素血清浓度（ME = -5.18，MAE = 6.63）。相对预测性能分析表明，传统模型和Wragge-Cooper模型在偏差或精密度方面没有显著差异（δME 1.17，δMAE -0.80）。对第1组患者个体化的氨基糖苷类药物和万古霉素消除进行回归分析，得出以下关系：万古霉素k10（1/h）= 0.081 + 1.037ke,amg，r = 0.73。使用第2组患者的数据，与传统模型相比，修订模型的偏差显著更小且更精确（δME -4.48；δMAE 1.22），并且偏差显著更小（δME 4.29），但不比Wragge-Cooper模型更精确（δMAE -0.58）。
修订模型是预测普通内科和重症监护病房人群中万古霉素血清浓度的准确方法。使用该模型能够在接受联合氨基糖苷类药物治疗的患者中实现万古霉素剂量个体化，并最大限度地减少万古霉素血清浓度监测。
