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患者群体中万古霉素的药代动力学:年龄、性别和体重的影响。

Vancomycin pharmacokinetics in a patient population: effect of age, gender, and body weight.

作者信息

Ducharme M P, Slaughter R L, Edwards D J

机构信息

Department of Pharmacy Practice, College of Pharmacy and Allied Health Professions, Wayne State University, Detroit, Michigan.

出版信息

Ther Drug Monit. 1994 Oct;16(5):513-8. doi: 10.1097/00007691-199410000-00013.

Abstract

The effects of age, gender, and body weight on the pharmacokinetics of vancomycin were examined using data collected as part of routine therapeutic drug monitoring in patients. One thousand eighty-five sets of steady-state peak and trough serum concentrations obtained from 704 different patients were used to calculate elimination rate constant (k), volume of distribution (V), and clearance (Cl) using a one-compartment model. The median half-life of vancomycin was 6.5 h. Clearance was significantly correlated with creatinine clearance as estimated using the Cockcroft-Gault equation [Cl = 0.771 (Clcr) + 18.9; r = 0.63]. V averaged 0.69 L/kg ideal body weight (IBW) with increased values in females, patients over age 60, and obese patients. V ranged from 0.58 L/kg IBW in normal weight males under age 40 to 1.17 L/kg IBW in obese females over age 60. V was not different in underweight patients and those of normal weight (43.8 vs. 44.4 L). Regression analysis indicated that V was more predictable in women than in men and that vancomycin distributed into excess body weight (EBW) to a greater extent in women. However, the correlation coefficients from multiple regression analysis of V with IBW, EBW, and age did not exceed 0.60, and the high root mean square error values of 11-15 L suggest considerable variability in V is not accounted for by these factors alone. Despite these limitations, dosing of vancomycin may be improved by adjusting initial estimates of V for patient age, gender, and obesity.

摘要

利用患者常规治疗药物监测收集的数据,研究了年龄、性别和体重对万古霉素药代动力学的影响。从704例不同患者中获取的1085组稳态峰浓度和谷浓度血清样本,采用一室模型计算消除速率常数(k)、分布容积(V)和清除率(Cl)。万古霉素的中位半衰期为6.5小时。清除率与使用Cockcroft - Gault方程估算的肌酐清除率显著相关[Cl = 0.771(Clcr)+ 18.9;r = 0.63]。V平均为0.69 L/kg理想体重(IBW),女性、60岁以上患者和肥胖患者的值升高。V范围从40岁以下正常体重男性的0.58 L/kg IBW到60岁以上肥胖女性的1.17 L/kg IBW。体重过轻患者和正常体重患者的V无差异(43.8对44.4 L)。回归分析表明,女性的V比男性更具可预测性,且万古霉素在女性体内向多余体重(EBW)的分布程度更大。然而,V与IBW、EBW和年龄的多元回归分析的相关系数不超过0.60,11 - 15 L的高均方根误差值表明这些因素单独无法解释V的显著变异性。尽管存在这些局限性,但通过根据患者年龄、性别和肥胖情况调整V的初始估计值,万古霉素的给药方案可能会得到改善。

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