Sequential updating of a new dynamic pharmacokinetic model for caffeine in premature neonates

Sandrine Micallef (1) , Billy Amzal (2) , Véronique Bach (3) , Karen Chardon (3) , Pierre Tourneux (4, 3) , Frédéric Y. Bois (1)

1 INERIS - Institut National de l'Environnement Industriel et des Risques
2 Novartis Pharma
3 PERITOX - Périnatalité et Risques Toxiques - UMR INERIS_I 1
4 Soins Intensifs de Néonatologie et Médecine Néonatale / Réanimation et Surveillance Continue de Pédiatrie [CHU Amiens]

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. 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. 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. This study provides the methodological basis to predict caffeine concentration in blood, after a given treatment if data are collected on the treated neonate.

Mots clés: PHARMACOKINETIC COMPARTMENTAL MODEL; POPULATION MODEL; BAYESIAN INFERENCE; MCMC ALGORITHMES; CAFFEINE; NEONATES

Domaines: Toxicologie; Sciences de l'environnement

Sandrine Micallef, Billy Amzal, Véronique Bach, Karen Chardon, Pierre Tourneux, et al.. Sequential updating of a new dynamic pharmacokinetic model for caffeine in premature neonates. Clinical Pharmacokinetics, 2007, 46 (1), pp.59-74. ⟨10.2165/00003088-200746010-00003⟩. ⟨ineris-00961910⟩