Microfluidic technology and simulation models in studying pharmacokinetics during pregnancy

Area of Science:

• Pharmacology
• Biomedical Engineering
• Reproductive Health

Background:

• Preterm birth and maternal/neonatal mortality necessitate better drug testing in pregnancy.
• Current models (2D/3D cell, animal) lack clinical translatability, excluding pregnant women from drug development.
• In silico and organ-on-a-chip platforms offer novel solutions for assessing therapeutic agents in pregnancy.

Purpose of the Study:

• To evaluate the utility of in silico simulation and microfluidic organ-on-a-chip platforms for drug pharmacokinetics in pregnancy.
• To compare drug transfer data from these novel platforms with traditional animal models.
• To assess the potential of these models to improve drug development for pregnant women.

Main Methods:

• Developed a multi-organ feto-maternal interface on-chip (FMi-PLA-OOC) with seven cell types to study drug pharmacokinetics.
• Tested pravastatin transfer across the FMi-PLA-OOC and compared it with in vivo animal and ex vivo placenta perfusion data.
• Utilized simulation software (Gastroplus®) to predict pregnant subject pharmacokinetics from nonpregnant data.

Main Results:

• Pravastatin transfer across the FMi-PLA-OOC and in silico models was approximately 18%.
• Animal models showed significantly higher drug accumulation (approx. 33%) in amniotic fluid.
• The novel platforms demonstrated similar and potentially more translatable pharmacokinetic predictions.

Conclusions:

• Feto-maternal interface on-chip (FMi-PLA-OOC) and in silico models are viable alternatives for studying pregnancy drug pharmacokinetics.
• These platforms provide valuable insights into placental drug transport and metabolism.
• The study offers a path to reduce "therapeutic orphans" and improve maternal/neonatal health outcomes by enhancing drug development for pregnant populations.