Improved Vancomycin Dosing in Children Using Area Under the Curve Exposure
| Autor: | Susan Cho, Edmund V. Capparelli, Jennifer Le, William Murray, Tri M. Tran, Gale L. Romanowski, Natalie Nguyen, Stephanie Natale, Tu T. Tran, John S. Bradley, Ivilynn Bui |
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| Rok vydání: | 2013 |
| Předmět: |
Male
Microbiology (medical) Pediatrics medicine.medical_specialty Adolescent Metabolic Clearance Rate Urology Microbial Sensitivity Tests Article Cohort Studies Young Adult chemistry.chemical_compound Pharmacokinetics Vancomycin Area under curve medicine Humans Trough Concentration Dosing Child Creatinine Models Statistical business.industry Area under the curve Infant Anti-Bacterial Agents Infectious Diseases chemistry Area Under Curve Child Preschool Pediatrics Perinatology and Child Health Female Creatinine blood business medicine.drug |
| Zdroj: | Pediatric Infectious Disease Journal. 32:e155-e163 |
| ISSN: | 0891-3668 |
| Popis: | 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.: 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.: 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 those12 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.: 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. |
| Databáze: | OpenAIRE |
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