Population pharmacokinetics of vancomycin in premature Malaysian neonates: identification of predictors for dosing determination

Lo, Y.; van Hasselt, J.G.C.; Heng, S.; Lim, C.; Lee, T.; Charles, B.G. (2010) Population pharmacokinetics of vancomycin in premature Malaysian neonates: identification of predictors for dosing determination. Antimicrobial agents and chemotherapy, 54 (6). pp. 2626-32. ISSN 1098-6596

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Abstract

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 > or =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 small-for-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 model-estimated pharmacokinetic parameter values.

Item Type: Article
Creators:
  1. Lo, Y.
  2. van Hasselt, J.G.C.
  3. Heng, S.
  4. Lim, C.
  5. Lee, T.
  6. Charles, B.G.
Journal or Publication Title: Antimicrobial agents and chemotherapy
Additional Information: Department of Pharmacy, Faculty of Medicine, University of Malaya, Lembah Pantai, Kuala Lumpur, Malaysia. yllo@um.edu.my
Uncontrolled Keywords: Anti-Bacterial Agents/administration & dosage* Anti-Bacterial Agents/blood; Anti-Bacterial Agents/pharmacokinetics; Gestational Age
Subjects: R Medicine
Divisions: Faculty of Medicine
Depositing User: Mr. Faizal Hamzah
Date Deposited: 06 May 2011 15:50
Last Modified: 21 Dec 2014 16:38
URI: http://eprints.um.edu.my/id/eprint/1226

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