Sequential updating of a new dynamic pharmacokinetic model for caffeine in premature neonates.
OBJECTIVE
Caffeine treatment is widely used in nursing care to reduce the risk of apnoea in premature neonates. To check the therapeutic efficacy of the treatment against apnoea, caffeine concentration in blood is an important indicator. The present study was aimed at building a pharmacokinetic model as a basis for a medical decision support tool.


METHODS
In the proposed model, time dependence of physiological parameters is introduced to describe rapid growth of neonates. To take into account the large variability in the population, the pharmacokinetic model is embedded in a population structure. The whole model is inferred within a Bayesian framework. To update caffeine concentration predictions as data of an incoming patient are collected, we propose a fast method that can be used in a medical context. This involves the sequential updating of model parameters (at individual and population levels) via a stochastic particle algorithm.


RESULTS
Our model provides better predictions than the ones obtained with models previously published. We show, through an example, that sequential updating improves predictions of caffeine concentration in blood (reduce bias and length of credibility intervals). The update of the pharmacokinetic model using body mass and caffeine concentration data is studied. It shows how informative caffeine concentration data are in contrast to body mass data.


CONCLUSIONS
This study provides the methodological basis to predict caffeine concentration in blood, after a given treatment if data are collected on the treated neonate.
Micallef
Sandrine
S
Institut National de l'Environnement Industriel et des Risques, Verneuil-en-Halatte, France. sandrine.micallef@ineris.fr
Amzal
Billy
B
Bach
Véronique
V
Chardon
Karen
K
Tourneux
Pierre
P
Bois
Frédéric Y
FY
D001499:Bayes Theorem; D002110:Caffeine / Q000493:pharmacokinetics*; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature
D002110:Caffeine