Taber David J, Fann Amy L, Malat Greg, Dupuis Robert E
Department of Pharmacy Services, Medical University of South Carolina, Charleston, USA.
Ther Drug Monit. 2003 Feb;25(1):67-72. doi: 10.1097/00007691-200302000-00010.
This study examined the pharmacokinetics and dosing requirements of vancomycin in adult liver transplant recipients and also evaluated the predictability of determining vancomycin-dosing requirements utilizing an estimated creatinine clearance (CrCl) approach. Twenty adult liver transplant recipients were included in this analysis. Vancomycin pharmacokinetic parameters and dosing requirements calculated from estimated CrCl and population-based pharmacokinetic equations were compared with values calculated using serum concentrations and assuming a one-compartment model. Compared with the values obtained using equations to estimate the CrCl and vancomycin pharmacokinetics (t, Cl, and Vd), the actual values were statistically different for half-life and clearance (11.0 vs. 16.4 hours and 52 vs. 36 mL/min, respectively; P < 0.01). Additionally, CrCl that were estimated using population-based formulas significantly overestimated actual CrCl calculated using 24-hour urine collections (65-78 vs. 43 mL/min; P < 0.05). The results from this study indicate that serum creatinine concentrations do not adequately predict glomerular filtration rates (GFR) or vancomycin clearance in adult liver transplant recipients. Based on these results, the use of 24-hour urine CrCl to predict GFR and serum concentrations to properly dose vancomycin is advocated.
本研究考察了万古霉素在成年肝移植受者中的药代动力学及给药需求，还评估了采用估算肌酐清除率（CrCl）方法来确定万古霉素给药需求的可预测性。本分析纳入了20名成年肝移植受者。将根据估算CrCl和基于群体的药代动力学方程计算出的万古霉素药代动力学参数及给药需求，与使用血清浓度并假定为一室模型计算出的值进行比较。与使用估算CrCl和万古霉素药代动力学（t、Cl和Vd）的方程得出的值相比，半衰期和清除率的实际值在统计学上存在差异（分别为11.0对16.4小时和52对36 mL/分钟；P < 0.01）。此外，使用基于群体的公式估算的CrCl显著高估了通过24小时尿液收集计算出的实际CrCl（65 - 78对43 mL/分钟；P < 0.05）。本研究结果表明，血清肌酐浓度无法充分预测成年肝移植受者的肾小球滤过率（GFR）或万古霉素清除率。基于这些结果，提倡使用24小时尿CrCl来预测GFR，并使用血清浓度来合理确定万古霉素的给药剂量。
