title: Bayesian pharmacokinetic analysis of a gentamicin nomogram in neonates: a retrospective study.
abstract: BACKGROUND
  Although gentamicin is used extensively within the first week of life for suspected sepsis in neonates, little is known about the performance of gentamicin dosing nomograms in this population.
  
  
  OBJECTIVE
  The goal of our study was to retrospectively assess the performance of a gentamicin dosing nomogram in neonates given gentamicin during the first week after birth.
  
  
  METHODS
  In this retrospective study, gentamicin therapeutic drug monitoring data were collected during routine clinical care for all neonates who were born in St. Boniface General Hospital (Winnipeg, Manitoba, Canada) between January 1999 and April 2001 and given gentamicin during the first week after birth. We used Bayesian pharmacokinetic analysis to retrospectively assess the performance of our gentamicin dosing nomogram in neonates born at gestation ages <32 weeks, between 32 and 34 weeks, and >34 weeks. Bayesian pharmacokinetic values for parameters within groups were compared and used to explore predicted peak and trough serum gentamicin concentrations based on the institutional dosing nomogram.
  
  
  RESULTS
  In a total of 58 neonates, those neonates born at ≤34 weeks' gestation had a weight-normalized apparent volume of gentamicin distribution 1.6 times larger than infants born after 34 weeks' gestation (P<0.001), as identified by Bayesian analysis. Weight-normalized gentamicin clearance was 22% lower in the youngest age category (P<0.01). Only 33% of predicted peak serum gentamicin concentrations were >6 mg/L for neonates born at ≤34 weeks' gestation, whereas 90% were therapeutic in neonates born at >34 weeks' gestation (P<0.001). With the present nomogram, the likelihood of an indication for adjustment of the dosing regimen was 12.4-fold higher (95% CI, 3.5-43.7) for those neonates born at ≤34 weeks' gestation.
  
  
  CONCLUSIONS
  These results have important clinical implications with regard to the advisability of determining peak serum gentamicin concentrations in neonates born at ≤34 weeks' gestation. Sampling of peak serum concentrations is indicated in this population to avoid underdosing and potential loss of therapeutic efficacy.
authors.affiliation: Department of Pharmacy, St. Boniface General Hospital, Winnipeg, Manitoba, Canada ; Faculty of Pharmacy, University of Manitoba, Winnipeg, Manitoba, Canada ; Department of Internal Medicine, University of Manitoba, Winnipeg, Manitoba, Canada ; Department of Pharmacology and Therapeutics, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: Robert E
authors.initials: RE
authors.lastname: Ariano
authors.affiliation: Faculty of Pharmacy, University of Manitoba, Winnipeg, Manitoba, Canada ; Department of Internal Medicine, University of Manitoba, Winnipeg, Manitoba, Canada ; Department of Pharmacology and Therapeutics, University of Manitoba, Winnipeg, Manitoba, Canada ; Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, Manitoba, Canada ; Centre on Aging, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Sitar
authors.affiliation: Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, Manitoba, Canada ; Department of Neonatology, St. Boniface General Hospital, Winnipeg, Manitoba, Canada.
authors.forename: Maria
authors.initials: M
authors.lastname: Davi
authors.affiliation: Department of Pharmacy, St. Boniface General Hospital, Winnipeg, Manitoba, Canada ; Faculty of Pharmacy, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: Sheryl A
authors.initials: SA
authors.lastname: Zelenitsky
keywords: Bayesian pharmacokinetics; gentamicin; neonatal sepsis; nomograms