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利用血清胱抑素 C 作为肾功能标志物的万古霉素群体药代动力学分析。

Population pharmacokinetic analysis of vancomycin using serum cystatin C as a marker of renal function.

机构信息

Division of Pharmacy, Ehime University Hospital, 454 Shitsukawa, Toon, Ehime 791-0295, Japan.

出版信息

Antimicrob Agents Chemother. 2010 Feb;54(2):778-82. doi: 10.1128/AAC.00661-09. Epub 2009 Nov 23.

Abstract

We determined the population pharmacokinetics of vancomycin (VAN) using the glomerular filtration rate (GFR) estimated from the serum cystatin C concentration. We examined the predictive performance of the trough serum VAN concentration for determination of the initial dose by using a new model for the analysis of the population pharmacokinetic parameters. Data for 86 patients were used to estimate the values of the population pharmacokinetic parameters. Analysis with a nonlinear mixed-effects modeling program was done by using a one-compartment model. Data for 78 patients were used to evaluate the predictive performance of the new model for the analysis of population pharmacokinetic parameters. The estimated GFR values determined by using Hoek's formula correlated linearly with VAN clearance (VAN clearance [ml/min]=0.825xGFR). The mean volume of distribution was 0.864 (liters/kg). The interindividual variability of VAN clearance was 19.8%. The accuracy of the prediction determined by use of the new model was statistically better than that determined by use of the Japanese nomogram-based model because the 95% confidence interval (-3.45 to -1.38) of the difference in each value of the mean absolute error (-2.41) did not include 0. Use of the serum cystatin C concentration as a marker of renal function for prediction of serum VAN concentrations may be useful.

摘要

我们使用血清胱抑素 C 浓度估算的肾小球滤过率(GFR)来确定万古霉素(VAN)的群体药代动力学。我们使用新的分析群体药代动力学参数模型来检查谷浓度血清 VAN 浓度对初始剂量的预测性能。使用 86 名患者的数据来估计群体药代动力学参数的价值。通过使用非线性混合效应建模程序进行分析,采用单室模型。使用 78 名患者的数据来评估新模型分析群体药代动力学参数的预测性能。使用 Hoek 公式确定的估计 GFR 值与 VAN 清除率呈线性相关(VAN 清除率[ml/min]=0.825xGFR)。平均分布体积为 0.864(升/千克)。VAN 清除率的个体间变异性为 19.8%。使用新模型确定的预测准确性在统计学上优于使用基于日本图表的模型确定的准确性,因为每个平均绝对误差(-2.41)值的差异的 95%置信区间(-3.45 至-1.38)不包括 0。使用血清胱抑素 C 浓度作为肾功能标志物预测血清 VAN 浓度可能是有用的。

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