Ducharme M P, Slaughter R L, Edwards D J
Department of Pharmacy Practice, College of Pharmacy and Allied Health Professions, Wayne State University, Detroit, Michigan.
Ther Drug Monit. 1994 Oct;16(5):513-8. doi: 10.1097/00007691-199410000-00013.
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.
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。
