title: Vancomycin pharmacokinetics and predicted dosage requirements in pediatric cancer patients.
abstract: OBJECTIVE
  To determine the pharmacokinetic parameters and compare pharmacodynamic target attainment at different dosing strategies of vancomycin in pediatric cancer patients.
  
  
  METHODS
  Pediatric patients who received vancomycin and had at least two steady-state concentrations taken within the same dosing interval were identified. Vancomycin minimum inhibitory concentrations (MICs) for methicillin resistant staphylococcus aureus (MRSA) isolates from our institution were determined using E-test. The population-based pharmacokinetic modeling was performed using NONMEM 7.2. A one-compartment model with first-order kinetics was used to estimate clearance (CL) and volume of distribution (Vd). Monte Carlo simulations (N = 9800) were performed to compare area-under-the-curve over 24 h (AUC24)/MIC and trough concentration at different doses.
  
  
  RESULTS
  Forty-nine patients, with 120 vancomcyin serum concentrations, were included in the analysis, mean age was 6 ± 2.5 (SD) years, mean weight was 19.6 ± 6.9(SD) kg, mean baseline serum creatinine was 0.4 ± 0.11(SD) mg/dl, and mean initial vancomycin dose was 205 mg/day (range 100-460). Final model pharmacokinetic parameters were: CL (L/h) = 0.381 × weight(0.75) and Vd (L) = 0.663 × weight. Mean baseline (±SD) vancomycin CL was 0.20 ± 0.07 L/h/kg and Vd 0.66 ± 0.001 L/kg. . Renal function, sex, age, stay in the intensive care unit, and co-administration of nephrotoxic medications did not have an effect on the calculated parameters. Using Monte Carlo simulation with reported MICs, a dose of 60 mg/kg/day achieved AUC24/MIC ≥400 and trough concentration ≥15 mcg/mL in only 21.5% and 11% of virtual subjects, respectively.
  
  
  CONCLUSIONS
  Higher than usual vancomycin doses may be required to treat serious MRSA infections in pediatric patients. The currently recommended dose of 60 mg/kg/day is unlikely to achieve the targets in most subjects. The optimal vancomycin dosing in pediatric cancer patients requires further investigations.
authors.affiliation: Novartis, Medical Affairs Department, Amman, Jordan.
authors.forename: Ola
authors.initials: O
authors.lastname: Abdel Hadi
authors.affiliation: Department of Pharmacy, King Hussein Cancer Center, Amman, Jordan somar@khcc.jo.
authors.forename: Suha
authors.initials: S
authors.lastname: Al Omar
authors.affiliation: Department of Pharmacy, King Hussein Cancer Center, Amman, Jordan.
authors.forename: Lama H
authors.initials: LH
authors.lastname: Nazer
authors.affiliation: Department of Infection Control, King Hussein Cancer Center, Amman, Jordan.
authors.forename: Sawsan
authors.initials: S
authors.lastname: Mubarak
authors.affiliation: Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, San Diego, CA, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Le
mesh_terms: D000293:Adolescent; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D054796:Drug Dosage Calculations; D005260:Female; D005544:Forecasting; D006801:Humans; D008297:Male; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects*; D008826:Microbial Sensitivity Tests / Q000379:methods; D009369:Neoplasms / Q000097:blood* / Q000188:drug therapy* / Q000453:epidemiology; D012189:Retrospective Studies; D013203:Staphylococcal Infections / Q000097:blood* / Q000188:drug therapy* / Q000453:epidemiology; D014640:Vancomycin / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics
chemical_list: D000900:Anti-Bacterial Agents; D014640:Vancomycin
keywords: Vancomycin; cancer; pediatrics; pharmacokinetics