PBPK Modeling Approach in Pregnant Subjects and Fetus

Authors: LeMerdy M, Nevarez J
Software: GastroPlus®
Division: Simulations Plus

PBPK modeling gives birth to a new application!

The impact of medication taken during pregnancy on both maternal and fetal health is a growing public health concern. The average number of prescription and over-the-counter medications taken by pregnant women increased by 68% between 1977 and 2007, with an average of over 4 active pharmaceutical ingredients (APIs) used during pregnancy!

An expansion of the PBPKPlus™ module in GastroPlus® by the Simulations Plus team enables the prediction of the pharmacokinetics (PK) of compounds in pregnant subjects. This model considers the critical differences in:
– tissue sizes
– blood flow rates
– enzyme expression levels
– glomerular filtration rates
– plasma protein binding
– other factors affected during pregnancy in both the maternal and fetal subjects

The expanded model was used to predict the PK of different compounds in pregnant subjects. The models were first verified against PK data in healthy non-pregnant volunteers and then applied to explain differences in the PK data for pregnant subjects.

Maxime Le Merdy, Sr. Scientist, Regulatory Strategies team, will carefully walk you through the methods and conclusions of PBPK modeling in pregnant subjects, including the fetal plasma concentrations and amniotic fluid concentrations predicted at different stages of pregnancy. This work describes the use of an emerging PBPK application in drug development. It demonstrates the ability to predict differences in PK in pregnant subjects for compounds excreted renally and/or metabolically cleared.

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