Background:
Drug prescriptions are usual during pregnancy, however, women and their fetuses still
remain an orphan population with regard to drugs efficacy and safety. Most xenobiotics diffuse through the placenta
and some of them can alter fetus development resulting in structural abnormalities, growth or functional
deficiencies.
Methods:
To summarize the different methodologies developed towards the prediction of fetal drug exposure.
Results:
Neonatal cord blood concentration is the most specific measurement of the transplacental drug transfer at
the end of pregnancy. Using the cord blood and mother drug concentrations altogether, drug exchanges between
the mother and fetus can be modeled and quantified via a population pharmacokinetic analysis. Thereafter, it is
possible to estimate the fetus exposure and the fetus-to-mother exposure ratio. However, the prediction of placental
transfer before any administration to pregnant women is desirable. Animal studies remain difficult to interpret
due to structural and functional inter-species placenta differences. The ex-vivo perfusion of the human placental
cotyledon is the method of reference to study the human placental transfer of drugs because it is thought to mimic
the functional placental tissue. However, extrapolation of data to in vivo situation remains difficult. Some research
groups have extensively worked on physiologically based models (PBPK) to predict fetal drug exposure
and showed very encouraging results.
Conclusion:
PBPK models appeared to be a very promising tool in order to predict fetal drug exposure in-silico.
However, these models mainly picture the end of pregnancy and knowledge regarding both, development of the
placental permeability and transporters is strongly needed.
Population Pharmacokinetic Model for Intravenous ASN100 in Healthy Subjects
