Limited predictability of amikacin clearance in extreme premature neonates at birth
Tóm tắt
Identify and quantify factors describing variability of amikacin clearance in preterm neonates at birth.
Population pharmacokinetics of amikacin were estimated in a cohort of 205 extreme preterm neonates [post conception age (PCA) 27.8, SD 1.8, range 24–30 weeks; weight 1.07, SD 0.34, range 0.45–1.98 kg, postnatal age < 72 h]. Covariate analysis included weight, PCA, Apgar score, prophylactic administration of a nonsteroidal anti‐inflammatory drug (NSAID) to the neonate, maternal indomethacin and betamethasone administration, and chorioamnionitis.
A one‐compartment linear disposition model with zero order input (0.3 h i.v. infusion) and first‐order elimination was used. The population parameter estimate for volume of distribution (
Size and post‐conception age are the major contributors to clearance variability in extreme premature neonates (<31 weeks PCA). The large (35% of total) unexplained variability in clearance reinforces the need for target concentration intervention to reduce variability in exposure to a safe and effective range.
Từ khóa
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