Pujal Meritxell, Soy Dolors, Codina Carles, Ribas Josep
Pharmacy Service (UASP), Hospital Clínic de Barcelona, University of Barcelona, Villarroel, 170, 08036 Barcelona, Spain.
Pharm World Sci. 2006 Aug;28(4):215-21. doi: 10.1007/s11096-006-9037-3. Epub 2006 Oct 26.
Hydrocephalus is usually resolved by diverting cerebrospinal fluid through a surgically implanted intra-ventricular catheter (shunt). The aim of this study was to characterize vancomycin pharmacokinetic (PK) parameters and optimal dosage in shunted patients under vancomycin treatment.
Intensive Care and Neurosurgical Units. University Hospital.
Retrospective data of vancomycin blood concentrations, demographics and biochemical parameters, from a Therapeutic Drug Monitoring (TDM) program, in ventricle-external shunted patients (Group A) and controls (Group B) were collected. In all subjects, several blood samples at steady state conditions were drawn. Individual PK parameters such as drug clearance (CL) and volume of distribution (V) were estimated by using an one-compartmental PK model and later, dosage regimens were individually adjusted by Bayesian analysis. The obtained CL and V mean +/- standard deviation were compared between both groups (A versus B). Vancomycin dosage regimens between both groups were also compared.
Patients demographics, clinical records, creatinine clearance by Cockcroft-Gault, vancomycin blood levels, vancomycin pK parameters and optimal initial IV vancomycin dosage.
Forty-five patients were included in the study: 15 patients in group A and 30 subjects in group B. Significant differences between CL(A) and CL(B) means were observed, while not between V(A) and V(B). In shunted patients, the required vancomycin daily dose to reach target concentrations was significantly higher than the dose needed in the control group (49.25 +/- 12.28 mg/kg/day vs. 31.74 +/- 6.70 mg/kg/day; P < 0.0005).
Greater vancomycin clearance was found in our shunted patients, thus they required higher vancomycin daily doses compared to the control group. Consequently, vancomycin TDM in shunted patients should be advisable in order to guarantee antibiotic blood concentrations within the recommended therapeutic range.
脑积水通常通过手术植入脑室内导管（分流管）来引流脑脊液得以解决。本研究的目的是描述万古霉素治疗下分流患者的药代动力学（PK）参数及最佳剂量。
重症监护病房和神经外科病房。大学医院。
收集来自治疗药物监测（TDM）项目的万古霉素血药浓度、人口统计学和生化参数的回顾性数据，这些数据来自脑室 - 体外分流患者（A组）和对照组（B组）。在所有受试者中，于稳态条件下采集多份血样。使用单室PK模型估算个体PK参数，如药物清除率（CL）和分布容积（V），随后通过贝叶斯分析对给药方案进行个体化调整。比较两组（A组与B组）获得的CL和V的均值±标准差。还比较了两组之间的万古霉素给药方案。
患者人口统计学、临床记录、Cockcroft - Gault法计算的肌酐清除率、万古霉素血药水平、万古霉素PK参数及最佳初始静脉注射万古霉素剂量。
本研究纳入45例患者：A组15例患者，B组30例受试者。观察到CL(A)和CL(B)均值之间存在显著差异，而V(A)和V(B)之间无显著差异。在分流患者中，达到目标浓度所需的万古霉素每日剂量显著高于对照组（49.25±12.28mg/kg/天 vs. 31.74±6.70mg/kg/天；P < 0.0005）。
我们的分流患者中发现万古霉素清除率更高，因此与对照组相比，他们需要更高的万古霉素每日剂量。因此，对分流患者进行万古霉素TDM是可取的，以确保抗生素血药浓度在推荐的治疗范围内。
