Viberg Anders, Lannergård Anders, Larsson Anders, Cars Otto, Karlsson Mats O, Sandström Marie
Division of Pharmokinetics and Drug Therapy, Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden.
Br J Clin Pharmacol. 2006 Sep;62(3):297-303. doi: 10.1111/j.1365-2125.2006.02652.x.
Since cefuroxime mainly is excreted by renal filtration, dosing is currently based on serum creatinine (Scr) or creatinine clearance (CLcr). However, it has been suggested that cystatin C (CysC) is superior to Scr as a marker of renal function. The aim of this prospective study was to develop a population model that describes the pharmacokinetics of cefuroxime and to investigate the usefulness of CysC as a covariate of the model parameters.
Ninety-seven patients were studied (CLcr range 6.5-115 ml min(-1)). Blood samples (n = 407) for the determination of cefuroxime were withdrawn according to a sparse data sampling schedule and analysed by liquid chromatography mass spectrometry. The population analysis was performed in NONMEM.
A two-compartment model described the data well. The biomarkers Scr, CLcr and CysC were evaluated as covariates on clearance (CL). The model that included CysC generated the best fit. In the final population model CL was a function of CysC and body weight, whereas V(1) was only a function of body weight. Final parameter estimates (relative standard errors) were 6.00 (3.2%) l h(-1), 11.4 (5.3%) l and 5.11 (11%) l for CL, V(1) and V(2), respectively.
Based on the results of the present study, and because CysC is practical to use in the clinic, it is suggested that individual dosing of cefuroxime may be based on CysC rather than on Scr or CLcr. Furthermore, our final population model may be useful as a tool when designing new dosing schedules for cefuroxime.
由于头孢呋辛主要通过肾脏滤过排泄，目前给药剂量是基于血清肌酐（Scr）或肌酐清除率（CLcr）。然而，有人提出胱抑素C（CysC）作为肾功能指标优于Scr。本前瞻性研究的目的是建立一个描述头孢呋辛药代动力学的群体模型，并研究CysC作为模型参数协变量的实用性。
研究了97例患者（CLcr范围为6.5 - 115 ml·min⁻¹）。根据稀疏数据采样计划采集用于测定头孢呋辛的血样（n = 407），并通过液相色谱 - 质谱法进行分析。群体分析在NONMEM中进行。
二室模型能很好地描述数据。生物标志物Scr、CLcr和CysC被评估为清除率（CL）的协变量。包含CysC的模型拟合最佳。在最终的群体模型中，CL是CysC和体重的函数，而V(1)仅是体重的函数。CL、V(1)和V(2)的最终参数估计值（相对标准误差）分别为6.00（3.2%）l·h⁻¹、11.4（5.3%）l和5.11（11%）l。
基于本研究结果，且由于CysC在临床中使用方便，建议头孢呋辛的个体化给药可基于CysC而非Scr或CLcr。此外，我们的最终群体模型在设计头孢呋辛新的给药方案时可能作为一种有用的工具。
