Introduction: The recent advance in using in silico tools, specially physiologically based pharmacokinetic model (PBPK), has improved our understanding on xenobiotics permeability through biological membrane. Pregnancy PBPK models that integrate longitudinal changes in maternal, placental, and fetal physiology during pregnancy in virtual population together with drugs properties can be applied to quantify transplacental passage and drugs exposure in different maternal and fetal organs [1].

Aim: To demonstrate the ability of pregnancy PBPK models to predict drug exposure in maternal, and umbilical plasma, the placental tissue, and fetal organs.

Method: The Simcyp Pregnancy Simulator was used to predict maternal, placenta, umbilical and fetal organs concentrations for cefuroxime, cefazolin, nifedipine, tenofovir, nelfinavir, and efavirenz [2-4]. Predictions were compared with observations, where available. Permeability through placenta was parametrized using experimental data.

Results: Observed concentrations were within the predicted 5th-95th intervals by the model. The derived PK parameters were also with 2-fold error criteria. Limited observed data on fetal organs exposure (2 compounds) fall in the model prediction space.

Conclusion: Pregnancy PBPK models provide valuable insights into xenobiotics disposition in special individuals that are otherwise difficult to study. These models are “live models” reflecting current knowledge, and their performance can be enhanced by utilizing data derived from advanced experimental tools, such as tissue on chips, ex vivo, and biopsy, to assess drug permeability through maternal, placenta and fetal biological barriers.