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

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.