The present study determined the pharmacokinetic profile of vancomycin in premature Malaysian infants. A one-compartment infusion model with first-order elimination was fitted to serum vancomycin concentration data (n ‫؍‬ 835 points) obtained retrospectively from the drug monitoring records of 116 premature newborn infants. Vancomycin concentrations were estimated by a fluorescence polarization immunoassay. Population and individual estimates of clearance and distribution volume and the factors which affected the variability observed for the values of these parameters were obtained using a population pharmacokinetic modeling approach. The predictive performance of the population model was evaluated by visual inspections of diagnostic plots and nonparametric bootstrapping with replacement. Dosing guidelines targeting a value of >400 for the area under the concentration-time curve over 24 h in the steady state divided by the MIC (AUC 24 /MIC ratio) were explored using Monte Carlo simulation. Body size (weight), postmenstrual age, and smallfor-gestational-age status are important factors explaining the between-subject variability of vancomycin pharmacokinetic parameter values for premature neonates. The typical population parameter estimates of clearance and distribution volume for a 1-kg premature appropriate-for-gestational-age neonate with a postmenstrual age of 30 weeks were 0.0426 liters/h and 0.523 liters, respectively. There was a 20% reduction in clearance for small-for-gestational-age infants compared to the level for the appropriate-for-gestational-age control. Dosage regimens based on a priori target response values were formulated. In conclusion, the pharmacokinetic parameter values for vancomycin in premature Malaysian neonates were estimated. Improved dosage regimens based on a priori target response values were formulated by incorporating body size, postmenstrual age, and small-for-gestational-age status, using Monte Carlo simulations with the modelestimated pharmacokinetic parameter values.Bacterial sepsis is a major cause of neonatal complications, prolonged hospital stay, and death in premature newborns, especially those in developing countries. Sepsis-related mortality and morbidity rates were even higher in extremely preterm neonates and intrauterine-growth-restricted infants because of their innate immunological immaturity (36). Because coagulase-negative staphylococcus (CoNS) is a common pathogen for late-onset (72-h-postbirth) septicemia, and because methicillin-resistant Staphylococcus aureus (MRSA) is an important pathogen (10), vancomycin continues to be widely prescribed in neonatal intensive care units.Kidney and vestibular/cochlear damage is a concern associated with vancomycin use. Very recently, it was shown that vancomycin trough concentrations were correlated with nephrotoxicity in hospitalized adult patients (27). Nonetheless, vancomycin-associated ototoxicity and nephrotoxicity among neonates are thought to be less frequent than those in adults (11), although more evidence-based i...