Altered XXXX pharmacokinetics in term neonates undergoing controlled @entity2332 .

@entity1 @entity801 @entity2806 @entity1763 @entity2332
AIM(S): Little is known about the pharmacokinetic (PK) properties of @entity801 in newborns undergoing controlled @entity2332 after suffering from @entity2806 due to perinatal @entity1763 . This study prospectively evaluates and describes the population PK of @entity801 in these @entity1 . METHODS: Demographic-, clinical-, and laboratory data of @entity1 included in a multicenter prospective observational cohort study (the "PharmaCool Study") were collected. A non-linear mixed-effects regression analysis (NONMEM(  ) ) was performed to describe the population PK of @entity801 . The most optimal dosing regimen was evaluated based on simulations of the final model. RESULTS: A total of 47 @entity1 receiving @entity801 were included in the analysis. The PK was best described by an allometric 2-compartment model with gestational age (GA) as a covariate on clearance (Cl). During @entity2332 the Cl of a typical @entity1 (3   kg, GA 40   weeks, 2   days post natal age (PNA)) was 0.06   L/kg   h(-1) (inter-individual variability (IIV) 26.6%) and volume of distribution of the central compartment (Vc) was 0.46   L   kg(-1) (IIV 40.8%). Cl was constant during @entity2332 and rewarming, but increased with 29% after reaching normothermia (>96   hours PNA). CONCLUSIONS: This study describes the PK of @entity801 in neonates undergoing controlled @entity2332 . The 29% higher Cl in the normothermic phase compared to the preceding phases suggests a delay in normalization of Cl after rewarming has occurred. Based on simulations we recommend an empiric dose of 5   mg   kg(-1) every 36   hours or every 24   hours for @entity1 with GA 36-40 weeks and GA 42   weeks, respectively. This article is protected by copyright. All rights reserved.
