Impact of a paediatric vial on the magnitude of systematic medication errors in neonates

Abstract

Purpose: A paediatric vial introduces additional costs and potential confusion when an adult vial already exists. The impact of a paediatric vial (amikacin 50 mg/ml) on pharmacokinetic parameter variability was compared to the variability associated with an adult vial (250 mg/ml). Methods: A population PK approach (NONMEM) was used to investigate clearance (CL) and volume of distribution (V) changes as markers of dose accuracy and variability from time-concentration profiles in 254 preterm neonates given intravenous amikacin. The paediatric vial was used in 56 and the adult vial in 198 neonates. Neonates had a mean gestational age (GA) of 28 weeks (range 24-30) and a mean weight of 1100 g (SD 33). Separate scale factors were applied to V and CL and their variability for neonates given a dose from the 50 mg/ml vial. Differences in V and CL parameter estimates and their variability before and after introduction of the 50 mg/ml vial reflect differences in dose administered and bioavailability. Results: There were more amikacin plasma concentrations in the target zone with the paediatric than the adult vial (72% and 58% respectively). The final model demonstrated an apparent 8% reduction in the estimate of V and a 29% reduction of its variability after introduction of the paediatric vial. Clearance was the same in neonates given adult or paediatric vials, but clearance variability was reduced by 53%. Conclusions: The introduction of a paediatric vial was associated with a reduction in observed variability of V and CL, reflecting unproved dosing precision. The 8% reduction in the estimate of V suggests that there may be differences in bioavailability between both types of vials when used in neonates due to dosing imprecision.