Lo, Y. and van Hasselt, J.G.C. and Heng, S. and Lim, C. and Lee, T. and 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. 2626-2632. ISSN 0066-4804, DOI 20385872.
Full text not available from this repository.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 |
|---|---|
| Funders: | UNSPECIFIED |
| 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 07:50 |
| Last Modified: | 07 Feb 2019 07:15 |
| URI: | http://eprints.um.edu.my/id/eprint/1226 |
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