| Population pharmacokinetics of vancomycin in premature Malaysian neonates: identification of predictors for dosing determination. | |
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MedLine Citation:
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PMID: 20385872 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Yoke-Lin Lo; Johan G C van Hasselt; Siow-Chin Heng; Chin-Theam Lim; Toong-Chow Lee; Bruce G Charles |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-04-12 |
Journal Detail:
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Title: Antimicrobial agents and chemotherapy Volume: 54 ISSN: 1098-6596 ISO Abbreviation: Antimicrob. Agents Chemother. Publication Date: 2010 Jun |
Date Detail:
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Created Date: 2010-05-18 Completed Date: 2010-09-14 Revised Date: 2011-03-03 |
Medline Journal Info:
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Nlm Unique ID: 0315061 Medline TA: Antimicrob Agents Chemother Country: United States |
Other Details:
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Languages: eng Pagination: 2626-32 Citation Subset: IM |
Affiliation:
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Department of Pharmacy, Faculty of Medicine, University of Malaya, Lembah Pantai, Kuala Lumpur, Malaysia. yllo@um.edu.my |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Anti-Bacterial Agents
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administration & dosage*,
blood,
pharmacokinetics* Gestational Age Humans Infant, Newborn Infant, Premature / blood* Infant, Small for Gestational Age / blood Malaysia Models, Biological Monte Carlo Method Retrospective Studies Sepsis / blood, drug therapy Statistics, Nonparametric Vancomycin / administration & dosage*, blood, pharmacokinetics* |
| Chemical | |
Reg. No./Substance:
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0/Anti-Bacterial Agents; 1404-90-6/Vancomycin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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