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.
No takes yet. Share an insight, caveat, or question.
Allegaert et al. (2006) studied this question.