title: Amikacin population pharmacokinetics among paediatric burn patients.
abstract: BACKGROUND
  The objectives of this study were to (1) determine the pharmacokinetics of amikacin among children with severe burn and (2) identify influential covariates.
  
  
  METHODS
  Population-based pharmacokinetic modelling was performed in NONMEM 7.2 for hospitalized children who received amikacin at 10-20mg/kg divided two, three, or four times per day as part of early empiric treatment of presumed burn-related sepsis.
  
  
  RESULTS
  The analysis included data from 70 patients (6 months to 17 years) with 282 amikacin serum concentrations. Amikacin's mean Cmax was 33.2±9.4μg/mL and the mean Cmin was 3.8±4.6μg/mL. The final covariate model estimated clearance as 5.98L/h/70kg (4.97-6.99, 95% CI), the volume of distribution in the central compartment as 16.7L/70kg (14.0-19.4, 95% CI), the volume of distribution in the peripheral compartment as 40.1L/70kg (15.0-80.4, 95% CI), and the inter-compartmental clearance as 3.38L/h/70kg (2.44-4.32, 95% CI). In multivariate analyses, current weight (P<0.001) was a significant covariate, while age, sex, height, serum creatinine, C-reactive protein, platelet count, the extent and type of burn, and concomitant vancomycin administration did not influence amikacin pharmacokinetics.
  
  
  CONCLUSIONS
  Children with burn featured elevated amikacin clearance when compared to healthy adult volunteers. However, peak amikacin concentrations are comparable to those attained in other critically-ill children, suggesting that elevated amikacin clearance may not result in sub-therapeutic antibacterial effects. In this study, we found that amikacin displays two-compartment pharmacokinetics, with weight exerting a strong effect upon amikacin clearance. Further pharmacodynamic studies are needed to establish the optimal dosing regimen for amikacin in paediatric burn patients.
authors.affiliation: Division of Clinical Pharmacology, Department of Paediatrics, University of Utah School of Medicine, Salt Lake City, Utah, United States. Electronic address: Catherine.Sherwin@hsc.utah.edu.
authors.forename: Catherine M T
authors.initials: CM
authors.lastname: Sherwin
authors.affiliation: James L. Winkle College of Pharmacy, University of Cincinnati, Cincinnati, Ohio, United States.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Wead
authors.affiliation: Division of Clinical Pharmacology, Department of Paediatrics, University of Utah School of Medicine, Salt Lake City, Utah, United States.
authors.forename: Chris
authors.initials: C
authors.lastname: Stockmann
authors.affiliation: James L. Winkle College of Pharmacy, University of Cincinnati, Cincinnati, Ohio, United States; The Shriners Hospitals for Children(®), Cincinnati, Ohio, United States.
authors.forename: Daniel
authors.initials: D
authors.lastname: Healy
authors.affiliation: Division of Clinical Pharmacology, Department of Paediatrics, University of Utah School of Medicine, Salt Lake City, Utah, United States.
authors.forename: Michael G
authors.initials: MG
authors.lastname: Spigarelli
authors.affiliation: Department of Surgery, University of Cincinnati, Cincinnati, Ohio, United States; The Shriners Hospitals for Children(®), Cincinnati, Ohio, United States.
authors.forename: Alice
authors.initials: A
authors.lastname: Neely
authors.affiliation: Department of Surgery, University of Cincinnati, Cincinnati, Ohio, United States; The Shriners Hospitals for Children(®), Cincinnati, Ohio, United States.
authors.forename: Richard
authors.initials: R
authors.lastname: Kagan
mesh_terms: D000293:Adolescent; D000583:Amikacin / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001830:Body Surface Area; D001835:Body Weight; D002056:Burns / Q000150:complications*; D002648:Child; D002675:Child, Preschool; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D015999:Multivariate Analysis; D012044:Regression Analysis; D018805:Sepsis / Q000150:complications / Q000188:drug therapy*; D014640:Vancomycin / Q000627:therapeutic use*
chemical_list: D000900:Anti-Bacterial Agents; D014640:Vancomycin; D000583:Amikacin
keywords: Amikacin; Paediatric burns; Pharmacokinetics