Dopamine Is An Indicator But Not An Independent Risk Factor For Reduced Amikacin Clearance In Elbw Infants

Introduction: Important interindividual variability in amikacin clearance was observed in preterm infants, only in part explain by gestational age (GA), birth weight or co-administration of non-selective cyclo-oxgenase (COX) inhibitor (1). 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 [<31 weeks gestational age (GA), early neonatal life, on respiratory support, 1/1/1999–1/6/2005]. Pharmacokinetics were calculated assuming a one-compartment model with instantaneous input and first order output based on paired samples collected for therapeutic drug monitoring before and following administration of the second dose. Monovariate analysis (Spearman, Mann-Whitney U) 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 in 240 neonates (mean GA 28 weeks, birth weight 1042g). 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 either GA, birth weight or co-treatment of a non-selective COX inhibitor were entered as second variable.

Conclusions: Dopamine is an indicator, but not an independent marker of reduced amikacin clearance in early neonatal life in ELBW-infants. Therefore, neither dose nor interval should be adjusted when dopamine is prescribed as soon as GA and co-administration of non-selective COX inhibitors were already taken into account.

(1) Allegaert et al. Br J Clin Pharmacol 2006;61:39–48