Population pharmacokinetics of vancomycin in premature Malaysian neonates: identification of predictors for dosing determination
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 pre...
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my.um.eprints.12262019-02-07T07:15:59Z http://eprints.um.edu.my/1226/ 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. R Medicine 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. American Society for Microbiology 2010-06 Article PeerReviewed 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 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2876370/ 20385872 |
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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. |
format |
Article |
author |
Lo, Y. van Hasselt, J.G.C. Heng, S. Lim, C. Lee, T. Charles, B.G. |
author_facet |
Lo, Y. van Hasselt, J.G.C. Heng, S. Lim, C. Lee, T. Charles, B.G. |
author_sort |
Lo, Y. |
title |
Population pharmacokinetics of vancomycin in premature Malaysian neonates: identification of predictors for dosing determination |
title_short |
Population pharmacokinetics of vancomycin in premature Malaysian neonates: identification of predictors for dosing determination |
title_full |
Population pharmacokinetics of vancomycin in premature Malaysian neonates: identification of predictors for dosing determination |
title_fullStr |
Population pharmacokinetics of vancomycin in premature Malaysian neonates: identification of predictors for dosing determination |
title_full_unstemmed |
Population pharmacokinetics of vancomycin in premature Malaysian neonates: identification of predictors for dosing determination |
title_sort |
population pharmacokinetics of vancomycin in premature malaysian neonates: identification of predictors for dosing determination |
publisher |
American Society for Microbiology |
publishDate |
2010 |
url |
http://eprints.um.edu.my/1226/ http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2876370/ |
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1643686692148740096 |
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13.18916 |