Population PK-guided simulation study in children exposed to drugs in human milk

Détails

ID Serval
serval:BIB_625295E90C95
Type
Actes de conférence (partie): contribution originale à la littérature scientifique, publiée à l'occasion de conférences scientifiques, dans un ouvrage de compte-rendu (proceedings), ou dans l'édition spéciale d'un journal reconnu (conference proceedings).
Sous-type
Abstract (résumé de présentation): article court qui reprend les éléments essentiels présentés à l'occasion d'une conférence scientifique dans un poster ou lors d'une intervention orale.
Collection
Publications
Titre
Population PK-guided simulation study in children exposed to drugs in human milk
Titre de la conférence
16th World Congress of Basic and Clinical Pharmacology
Auteur(s)
Ito S., Garcia-Bournissen F., Panchaud A., Csajka C., Kristensen J., Taddio A., Ilett K., Begg E., Tomlinson G.
Adresse
Copenhagen, Denmark, 17-23 July, 2010
ISBN
1742-7843
Statut éditorial
Publié
Date de publication
2010
Peer-reviewed
Oui
Volume
107
Série
Basic and Clinical Pharmacology and Toxicology
Pages
40
Langue
anglais
Résumé
Risks of significant infant drug exposure through human milk arepoorly defined due to lack of large-scale PK data. We propose to useBayesian approach based on population PK (popPK)-guided modelingand simulation for risk prediction. As a proof-of-principle study, weexploited fluoxetine milk concentration data from 25 women. popPKparameters including milk-to-plasma ratio (MP ratio) were estimatedfrom the best model. The dose of fluoxetine the breastfed infant wouldreceive through mother's milk, and infant plasma concentrations wereestimated from 1000 simulated mother-infant pairs, using randomassignment of feeding times and milk volume. A conservative estimateof CYP2D6 activity of 20% of the allometrically-adjusted adult valuewas assumed. Derived model parameters, including MP ratio were consistentwith those reported in the literature. Visual predictive check andother model diagnostics showed no signs of model misspecifications.The model simulation predicted that infant exposure levels to fluoxetinevia mother's milk were below 10% of weight-adjusted maternal therapeuticdoses in >99% of simulated infants. Predicted median ratio ofinfant-mother serum levels at steady state was 0.093 (range 0.033-0.31),consistent with literature reported values (mean=0.07; range 0-0.59).Predicted incidence of relatively high infant-mother ratio (>0.2) ofsteady-state serum fluoxetine concentrations was <1.3%. Overall, ourpredictions are consistent with clinical observations. Our approach maybe valid for other drugs, allowing in silico prediction of infant drugexposure risks through human milk. We will discuss application of thisapproach to another drug used in lactating women.
Création de la notice
30/05/2011 17:02
Dernière modification de la notice
20/08/2019 14:19
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