Thomson A H, Staatz C E, Tobin C M, Gall M, Lovering A M
Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, Scotland, UK.
J Antimicrob Chemother. 2009 May;63(5):1050-7. doi: 10.1093/jac/dkp085. Epub 2009 Mar 19.
The aims of this study were to develop a population pharmacokinetic model of vancomycin in adult patients, to use this model to develop dosage guidelines targeting vancomycin trough concentrations of 10-15 mg/L and to evaluate the performance of these new guidelines.
All data analyses were performed using NONMEM. A population pharmacokinetic model was first developed from vancomycin dosage and concentration data collected during routine therapeutic drug monitoring in 398 patients, then new vancomycin dosage guidelines were devised by using the model to predict vancomycin trough concentrations in a simulated dataset. Individual estimates of CL and V1 were then obtained in an independent group of 100 patients using the population model and the POSTHOC option. These individual estimates were used to predict vancomycin trough concentrations and steady-state AUC(24)/MIC ratios using the current and new dosage guidelines.
The population analysis found that the vancomycin data were best described using a bi-exponential elimination model with a typical CL of 3.0 L/h that changed by 15.4% for every 10 mL/min difference from a CL(CR) of 66 mL/min. V(ss) was 1.4 L/kg. The proposed dosage guidelines were predicted to achieve 55% of vancomycin troughs within 10-15 mg/L and 71% within 10-20 mg/L, which is significantly higher than current guidelines (19% and 22%, respectively). The proportion of AUC(24)/MIC ratios above 400 was also higher, 87% compared with 58%.
New vancomycin dosage guidelines have been developed that achieve trough concentrations of 10-15 mg/L earlier and more consistently than current guidelines.
本研究旨在建立成人患者万古霉素的群体药代动力学模型，利用该模型制定目标万古霉素谷浓度为10 - 15mg/L的给药指南，并评估这些新指南的性能。
所有数据分析均使用NONMEM进行。首先根据398例患者在常规治疗药物监测期间收集的万古霉素剂量和浓度数据建立群体药代动力学模型，然后使用该模型预测模拟数据集中的万古霉素谷浓度，从而制定新的万古霉素给药指南。随后，在一个由100名患者组成的独立组中，使用群体模型和POSTHOC选项获得个体的清除率（CL）和中央室容积（V1）估计值。这些个体估计值用于根据当前和新的给药指南预测万古霉素谷浓度和稳态血药浓度-时间曲线下面积（AUC(24)）/最低抑菌浓度（MIC）比值。
群体分析发现，万古霉素数据最好用双指数消除模型描述，典型清除率为3.0L/h，每10mL/min的肌酐清除率（CL(CR)）差异导致清除率变化15.4%。稳态分布容积（V(ss)）为1.4L/kg。预计新的给药指南能使55%的万古霉素谷浓度达到10 - 15mg/L，71%达到10 - 20mg/L，显著高于当前指南（分别为19%和22%）。AUC(24)/MIC比值高于400的比例也更高，分别为87%和58%。
已制定出新的万古霉素给药指南，与当前指南相比，能更早、更稳定地达到10 - 15mg/L的谷浓度。
