Dopamine is not an independent risk factor for reduced amikacin clearance in extremely low-birth-weight infants.

Introduction: Important inter-individual variability in amikacin clearance was observed in preterm infants, only in part explained by gestational age (GA), birth weight, or coadministration of nonselective cyclo-oxygenase (COX) inhibitor. We therefore evaluated whether dopamine had an additional effect on amikacin clearance.

Methods: Clinical characteristics (GA, weight, COX inhibitor, dopamine, prenatal betamethasone) and amikacin pharmacokinetics were retrospectively collected in a cohort of preterm infants (GA of <31 wks, early neonatal life on respiratory support, between January 1, 1999 and January 6, 2005). Pharmacokinetics were calculated by assuming a one-compartment model with instantaneous input and first-order output based on paired samples collected for therapeutic drug monitoring before and following second administration. Monovariate analysis (Spearman, Mann-Whitney U test) was used to study the impact of clinical characteristics on amikacin clearance, and logistic regression was used to assess their potential independent effect.

Results: Paired amikacin samples were available for 240 neonates (mean GA, 28 wks; birth weight, 1042 g). Amikacin clearance was 0.46 (range, 0.09-2.33) mL/kg/min and distribution volume was 0.54 (range, 0.17-2.31) L/kg. GA, birth weight, COX inhibitor, and dopamine had a significant effect on amikacin clearance. In a logistic regression model, dopamine was no longer a significant variable when GA, birth weight, or cotreatment of a nonselective COX inhibitor was entered as second variable.

Conclusions: Dopamine is an indicator but not an independent marker of reduced amikacin clearance in early neonatal life in extremely low-birth-weight infants. Therefore, neither dose nor interval should be adapted when dopamine is prescribed, if GA and coadministration of nonselective COX inhibitors already have been taken into account.