Population Pharmacokinetic Modeling in the Presence of Missing Time-Dependent Covariates: Impact of Body Weight on Pharmacokinetics of Paracetamol in Neonates.

ABSTRACT: Body weight is the primary covariate in pharmacokinetics of many drugs and dramatically changes during the first weeks of life of neonates. The objective of this study is to determine if missing body weights in preterm and term neonates affect estimates of model parameters and which methods can be used to improve performance of a population pharmacokinetic model of paracetamol. Data for our analysis were obtained from previously published studies on the pharmacokinetics of intravenous paracetamol in neonates. We adopted a population model of body weight change in neonates to implement three previously introduced methods of handling missing covariates based on data imputation, likelihood function modification, and full random effects modeling. All models were implemented in NONMEM 7.4, and

SUBMITTER: Krzyzanski W 

PROVIDER: S-EPMC6820681 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature