PBPK Modeling Approach to Predict the Behavior of Drugs Cleared by Metabolism in Pregnant Subjects and Fetuses.

ABSTRACT: This study aimed to develop a physiologically based pharmacokinetic (PBPK) model that simulates metabolically cleared compounds' pharmacokinetics (PK) in pregnant subjects and fetuses. This model accounts for the differences in tissue sizes, blood flow rates, enzyme expression levels, plasma protein binding, and other physiological factors affecting the drugs' PK in both the pregnant woman and the fetus. The PBPKPlus™ module in GastroPlus^® was used to model the PK of metoprolol, midazolam, and metronidazole for both non-pregnant and pregnant groups. For each of the three compounds, the model was first developed and validated against PK data in healthy non-pregnant volunteers and then applied to predict the PK in the pregnant groups. The model accurately described the PK in both

SUBMITTER: Le Merdy M 

PROVIDER: S-EPMC10820132 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature