title: Gentamicin pharmacokinetics in neonates with patent ductus arteriosus.
abstract: OBJECTIVE
  To determine the effect of patent ductus arteriosus on the pharmacokinetics of gentamicin in neonates and to examine whether any particular pharmacokinetic parameter is of value as a marker of patent ductus arteriosus.
  
  
  METHODS
  Cohort study of neonates treated with gentamicin, according to a standard dosing protocol.
  
  
  METHODS
  A 24-bed, Level III, neonatal intensive care unit.
  
  
  METHODS
  Neonates treated with gentamicin at the time of admission to the neonatal intensive care unit, using a standard protocol, and who were < 36 wks of gestational age.
  
  
  METHODS
  All patients received a gentamicin loading dose, and had gentamicin concentrations measured at 2 and 12 hrs after this dose, in order to determine pharmacokinetic parameters and calculate the optimum maintenance dose. Those neonates subsequently diagnosed to have patent ductus arteriosus, based on clinical suspicion and echocardiographic confirmation, were compared with those neonates without clinically suspected patent ductus arteriosus. Gentamicin pharmacokinetic parameters were calculated using a one-compartment model.
  
  
  RESULTS
  A total of 322 courses of gentamicin were administered (patent ductus arteriosus, n = 106; control, n = 216). Gentamicin clearance was decreased in the patent ductus arteriosus group vs. the control group (40.02 vs. 44.73 mL/kg/hr; p < .0108). Volume of distribution was greater for patent ductus arteriosus patients (0.61 L/kg) than for controls (0.54 L/kg) (p < .0002). Also, volume of distribution was a useful marker for presence of patent ductus arteriosus, with a 92% specificity for patent ductus arteriosus.
  
  
  CONCLUSIONS
  Gentamicin dosing should be altered in neonates with patent ductus arteriosus to reflect the impact of higher volume of distribution and lower clearance. When the gentamicin volume of distribution exceeds 0.7 L/kg, it may be of predictive value for the presence of patent ductus arteriosus.
authors.affiliation: School of Pharmacy, University of North Carolina at Chapel Hill, USA.
authors.forename: B S
authors.initials: BS
authors.lastname: Williams
authors.forename: J L
authors.initials: JL
authors.lastname: Ransom
authors.forename: P
authors.initials: P
authors.lastname: Gal
authors.forename: R Q
authors.initials: RQ
authors.lastname: Carlos
authors.forename: M
authors.initials: M
authors.lastname: Smith
authors.forename: S A
authors.initials: SA
authors.lastname: Schall
mesh_terms: D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D015331:Cohort Studies; D004374:Ductus Arteriosus, Patent / Q000378:metabolism*; D005839:Gentamicins / Q000493:pharmacokinetics* / Q000627:therapeutic use; D005865:Gestational Age; D006801:Humans; D007231:Infant, Newborn; D007262:Infusions, Intravenous; D007363:Intensive Care Units, Neonatal; D011237:Predictive Value of Tests
chemical_list: D000900:Anti-Bacterial Agents; D005839:Gentamicins