Document Detail


Improved vancomycin dosing in children using area under the curve exposure.
MedLine Citation:
PMID:  23340565     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: : Our objectives were to (1) determine the pharmacokinetic indices of vancomycin in pediatric patients; and (2) compare attainment of 2 target exposures: area under curve (AUC) / minimum inhibitory concentration (MIC) ≥400 and trough concentration ≥15 mcg/mL.
METHODS: : The population-based pharmacokinetic modeling was performed using NONMEM 7.2 for children ≥3 months old who received vancomycin for ≥48 hours from 2003 to 2011. A 1-compartment model with first-order kinetics was used to estimate clearance, volume of distribution and AUC. Empiric Bayesian post hoc individual parameters and Monte Carlo simulations (N = 11,000) were performed.
RESULTS: : Analysis included 702 patients with 1660 vancomycin serum concentrations. Median age was 6.6 (interquartile range 2.2-13.4) years, weight 22.7 (12.6-46) kg and baseline serum creatinine 0.40 (0.30-0.60) mg/dL. Final model pharmacokinetic indices were clearance (L/h) = 0.248 * Wt * (0.48/serum creatinine) * (ln(age)/7.8) and volume of distribution (L) = 0.636 * Wt. Using these parameters and the observed MIC distribution, Monte Carlo simulation indicated that the initial median dose of 44 (39-52) mg/kg/day was inadequate in most subjects. Regimens of 60 mg/kg/day for subjects ≥12 years old and 70 mg/kg/day for those <12 years old achieved target AUC/MIC in ~75% and trough concentrations ≥15 in ~45% of virtual subjects. An AUC/MIC ~400 corresponded to trough concentration ~8 to 9 mcg/mL.
CONCLUSIONS: : Targeted exposure using vancomycin AUC/MIC, compared with trough concentrations, is a more realistic target in children. Depending on age, serum creatinine and MIC distribution, vancomycin in a dosage of 60 to 70 mg/kg/day was necessary to achieve AUC/MIC ≥ 400 in 75% of patients.
Authors:
Jennifer Le; John S Bradley; William Murray; Gale L Romanowski; Tu T Tran; Natalie Nguyen; Susan Cho; Stephanie Natale; Ivilynn Bui; Tri M Tran; Edmund V Capparelli
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Pediatric infectious disease journal     Volume:  32     ISSN:  1532-0987     ISO Abbreviation:  Pediatr. Infect. Dis. J.     Publication Date:  2013 Apr 
Date Detail:
Created Date:  2013-04-04     Completed Date:  2013-09-11     Revised Date:  2014-04-02    
Medline Journal Info:
Nlm Unique ID:  8701858     Medline TA:  Pediatr Infect Dis J     Country:  United States    
Other Details:
Languages:  eng     Pagination:  e155-63     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Adolescent
Anti-Bacterial Agents / administration & dosage*,  pharmacokinetics*
Area Under Curve
Child
Child, Preschool
Cohort Studies
Creatinine / blood
Female
Humans
Infant
Male
Metabolic Clearance Rate
Microbial Sensitivity Tests
Models, Statistical
Vancomycin / administration & dosage*,  pharmacokinetics*
Young Adult
Grant Support
ID/Acronym/Agency:
K23 AI089978/AI/NIAID NIH HHS; K23AI089978/AI/NIAID NIH HHS; U54 HD071600/HD/NICHD NIH HHS; U54HD071600/HD/NICHD NIH HHS
Chemical
Reg. No./Substance:
0/Anti-Bacterial Agents; 6Q205EH1VU/Vancomycin; AYI8EX34EU/Creatinine
Comments/Corrections

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