GENTAMICIN PHARMACOKINETICS IN NEONATES WITH PATENT DUCTUS-ARTERIOSUS

Objectives: 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 paten t ductus arteriosus. Design: Cohort study of neonates treated with gen tamicin, according to a standard dosing protocol. Setting: A 24-bed, L evel III, neonatal intensive care unit. Patients: Neonates treated wit h gentamicin at the time of admission to the neonatal intensive care u nit, using a standard protocol, and who were <36 wks of gestational ag e. Interventions: All patients received a gentamicin loading dose, and had gentamicin concentrations measured at 2 and 12 hrs after this dos e, in order to determine pharmacokinetic parameters and calculate the optimum maintenance dose. Those neonates subsequently diagnosed to hav e patent ductus arteriosus, based on clinical suspicion and echocardio graphic confirmation, were compared with those neonates without clinic ally suspected patent ductus arteriosus. Gentamicin pharmacokinetic pa rameters were calculated using a one-compartment model. Measurements a nd Main Results: A total of 322 courses of gentamicin were administere d (patent ductus arteriosus, n = 106; control, n = 216). Gentamicin cl earance was decreased in the patent ductus arteriosus group vs. the co ntrol group (40.02 vs. 44.73 mL/ kg/hr; p < .0108). Volume of distribu tion was greater for patent ductus arteriosus patients(0.61 L/kg) than for controls (0.54 L/kg) (p < .0002). Also, Volume of distribution wa s a useful marker for presence of patent ductus arteriosus, with a 92% specificity for patent ductus arteriosus.Conclusions: Gentamicin dosi ng should be altered in neonates with patent ductus arteriosus to refl ect the impact of higher volume of distribution and lower clearance. W hen the gentamicin volume of distribution exceeds 0.7 L/kg, it may be of predictive value for the presence of patent ductus arteriosus.