Pharmacokinetics of gentamicin in neonates on extracorporeal membrane oxygenation

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Abstract
Extracorporeal membrane oxygenation (ECMO) has been used in more than 1,000 infants in 50 centers in the United States. The extracorporeal circuit contains approximately 400 ml of blood, an amount exceeding the blood volume of most full-term neonates. The effect of this additional blood volume on drug disposition is unknown. In this study, we determined the pharmacokinetic parameters of gentamicin in 10 infants on ECMO. Gentamicin concentrations were determined by a fluorescence polarization immunoassay. Pharmacokinetic parameters were determined from these concentrations by using a two-compartment model. Our study demonstrated a mean steady-state volume of distribution of 0.51 +/- 0.11 liters/kg, a figure similar to that in previous studies of full-term infants. The elimination half-life was found to be prolonged (mean, 573 +/- 263 min). The creatinine level in the plasma of the infants was found to be a statistically significant predictor of elimination half-life. Recommendations regarding initial dosing levels of gentamicin in infants on ECMO are made.