Document Detail


Population pharmacokinetics of vancomycin in premature Malaysian neonates: identification of predictors for dosing determination.
MedLine Citation:
PMID:  20385872     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Yoke-Lin Lo; Johan G C van Hasselt; Siow-Chin Heng; Chin-Theam Lim; Toong-Chow Lee; Bruce G Charles
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-04-12
Journal Detail:
Title:  Antimicrobial agents and chemotherapy     Volume:  54     ISSN:  1098-6596     ISO Abbreviation:  Antimicrob. Agents Chemother.     Publication Date:  2010 Jun 
Date Detail:
Created Date:  2010-05-18     Completed Date:  2010-09-14     Revised Date:  2013-05-29    
Medline Journal Info:
Nlm Unique ID:  0315061     Medline TA:  Antimicrob Agents Chemother     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2626-32     Citation Subset:  IM    
Affiliation:
Department of Pharmacy, Faculty of Medicine, University of Malaya, Lembah Pantai, Kuala Lumpur, Malaysia. yllo@um.edu.my
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MeSH Terms
Descriptor/Qualifier:
Anti-Bacterial Agents / 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:
0/Anti-Bacterial Agents; 1404-90-6/Vancomycin
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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