Guay D R, Vance-Bryan K, Gilliland S, Rodvold K, Rotschafer J
Section of Clinical Pharmacy, St. Paul-Ramsey-Medical Center, MN 55101.
J Clin Pharmacol. 1993 Oct;33(10):918-22. doi: 10.1002/j.1552-4604.1993.tb01922.x.
Limited data have been published that compare the pharmacokinetic parameters of vancomycin in elderly versus young patients. This study was designed to assess vancomycin pharmacokinetics in 148 elderly (> or = 60 years of age) and 140 young (18-59 years of age) hospitalized infected patients. Serum vancomycin concentrations were determined using fluorescence polarization immunoassay. Serum concentration-versus-time data were fitted to a two-compartment Bayesian forecasting program. Elderly versus young vancomycin pharmacokinetic parameters derived were as follows (patients with serum creatinine < or = 1.5 mg/dL); mean +/- standard deviation terminal disposition half-life (t1/2) of 17.8 +/- 11.8 versus 7.5 +/- 6.7 hours, respectively, P < .05; volume of distribution (Vz) of 74.2 +/- 32.3 versus 67.0 +/- 30.7 L, respectively, P = .16; and total body clearance (CL) of 0.71 +/- 0.41 versus 1.22 +/- 0.50 mL/min/kg, respectively, P < .05. Comparing subjects with normal serum creatinine values (< or = 1.5 mg/dL), the elderly required smaller daily doses as compared with the young group to maintain target peak and trough vancomycin serum concentrations (18.2 +/- 5.8 verus 25.2 +/- 7.8 mg/kg/day, P < .05). Stepwise multiple regression models for the pharmacokinetic parameters were developed to assess the predictive power of age, controlling for the effects of gender, total body weight, serum creatinine, and creatinine clearance. Age was consistently an independent and significant predictor of t1/2, Vz, and CL. These data demonstrate that elderly patients exhibit significant differences in vancomycin pharmacokinetic parameters compared with young patients and constitute a patient population in need of individualized vancomycin dosing due to substantial heterogeneity in physiologic and pharmacokinetic parameters.
已发表的比较万古霉素在老年患者与年轻患者中药代动力学参数的数据有限。本研究旨在评估148例老年(≥60岁)和140例年轻(18 - 59岁)住院感染患者的万古霉素药代动力学。采用荧光偏振免疫分析法测定血清万古霉素浓度。将血清浓度 - 时间数据拟合到双室贝叶斯预测程序。得出的老年与年轻患者万古霉素药代动力学参数如下(血清肌酐≤1.5mg/dL的患者);平均±标准差的终末处置半衰期(t1/2)分别为17.8±11.8小时和7.5±6.7小时,P <.05;分布容积(Vz)分别为74.2±32.3L和67.0±30.7L,P = 0.16;总体清除率(CL)分别为0.71±0.41和1.22±0.50mL/min/kg,P <.05。与血清肌酐值正常(≤1.5mg/dL)的受试者相比,老年患者维持万古霉素血清峰浓度和谷浓度所需的每日剂量比年轻组小(18.2±5.8对25.2±7.8mg/kg/天,P <.05)。建立了药代动力学参数的逐步多元回归模型,以评估年龄的预测能力,同时控制性别、总体重、血清肌酐和肌酐清除率的影响。年龄始终是t1/2、Vz和CL的独立且显著的预测因子。这些数据表明,与年轻患者相比,老年患者在万古霉素药代动力学参数上存在显著差异,并且由于生理和药代动力学参数存在很大异质性,老年患者是需要个体化万古霉素给药的患者群体。