摘要
目的 :比较国产去甲万古霉素在老年人和年轻人中的体内过程 ,为制订去甲万古霉素在治疗老年人感染时的合理给药方案提供依据 ;建立快捷、实用的去甲万古霉素治疗药物监测 (TDM)方法。方法 :同期对照研究去甲万古霉素在 1 0名健康老年受试者 (老年组 )和 1 0名健康年轻受试者 (年轻组 )中的药代动力学。以微生物法和荧光偏振免疫法 (FPIA)测定血药浓度 ,以微生物法测定尿药浓度。结果 :老年组和年轻组静脉滴注去甲万古霉素 80 0mg后的体内过程均符合二室模型。与年轻组比较 ,老年组表观分布容积 (Vd)增大 ,总清除率 (CLt)及肾清除率 (CLr)降低 ,药时曲线下面积 (AUC)增加和消除半衰期(t1 /2 β)延长。以上各项药代参数在两组间差异均具非常显著性 (P <0 .0 1 ) ;两组血药峰浓度相近 (P >0 .0 5 )。去甲万古霉素给药后 1 2h内的累积尿排出率老年组较年轻组明显为低 ,分别为 (77.1 3± 8.95 ) %和 (83.82± 1 6 .80 ) % (P <0 .0 1 ) ,但给药后4 8h两组的累积尿排出率相近 ,分别为 (85 .38± 8.6 2 ) %和 (86 .1 2± 1 6 .85 ) % ,两组差异无显著性 (P >0 .0 5 )。以微生物法和FPIA同时测定去甲万古霉素血清标本。两种测定方法测得结果呈良好线性相关性。线性回归方程为Y =0 .75 34X - 0 .5 94 8(Y
Objective: To compare the clinical pharmacokinetics of norvancomycin in the elderly and young people in order to provide data for its rational use in the elderly; and to establish a rapid method for therapeutic drug monitoring (TDM) of norvancomycin. Methods: Pharmacokinetics study of norvancomycin was performed in 10 healthy elderly volunteers and 10 healthy young volunteers, the results were compared. A single dose of 800 mg norvancomycin was administered by intravenous infusion. Serum concentrations were determined by both bioassay and fluorescence polarization immunoassay (FPIA), a urine concentrations were determined by bioassay. Results: The serum concentration time curves of norvancomycin were fitted in two compartment model in both two groups. Compared with young group, the distribution volume (V d) and AUC were increased, total clearance (CL t) and renal clearance (CL r) were lower and the elimination half life (T 1/2β ) were longer in the elderly group. The differences of these pharmacokinetic parameters between the two groups were statistically significant ( P <0.01) except the peak serum concentrations. The cumulative urinary excretion rate within 12 h after iv infusion in the elderly group was much lower than that in the young group ( P <0.01), being (77.13±8.95)% and (83.82±16.80)% respectively, but the figures within 48 h after iv infusion being (85.38±8.62)% and (86.12±16.85)% respectively, which were not significantly different( P> 0.05). A good linear correlation was demonstrated between norvancomycin serum concentrations measured by bioassay and FPIA, which fitted the equation: Y=0.7534X-0.5948 (Y:bioassay method ;X: FPIA method;R 2=0.9703). Conclusions: For the treatment of infections in the elderly, novancomycin should be used with increased interval or decreased dose and TDM is required. FPIA is a rapid, accurate and specific method for the assay of serum concentration of norvancomycin.
出处
《中国抗感染化疗杂志》
2003年第4期202-205,共4页
Chinese Journal of Infection and Chemotherapy
