Vancomycin pharmacokinetics in infants: relationships to indices of maturation.

The relationships between steady state pharmacokinetics of vancomycin and various indices of maturation were examined in 11 infants (gestational ages, 27 to 40 weeks; postconceptional ages (PCA), 29 to 48 weeks). Vancomycin was administered as a 10-mg/kg iv infusion over 30 minutes. Serial blood samples were obtained over a dosage interval and vancomycin serum concentrations were determined by fluorescence polarization immunoassay. Model-independent pharmacokinetic data analysis yielded values for vancomycin systemic clearance (CL), volume of distribution (Vdss) and half-life ranging from 0.032 to 0.484 liter/hour, 0.44 to 2.5 liters and 3.5 to 9.6 hours respectively. Stepwise multiple regression analysis indicated that PCA was the best single variable model to predict vancomycin clearance as described, namely: CL (liters/hour) = 0.0224 PCA (weeks) - 0.639 (r = 0.91; P less than 0.0001). Other more complex models using a combination of patient variables only modestly improved the ability to explain the variability in vancomycin clearance. Vdss was strongly related to body weight (r = 0.93; P less than 0.0001) Vdss = 0.563 weight (kg) + 0.052). Our results suggest that postnatal alterations in vancomycin disposition are related to maturational changes in body composition and renal function. These data also suggest that vancomycin doses smaller than those previously recommended may be used to achieve therapeutic steady state vancomycin serum concentrations during the first 2 months of life.