In vitro study of pharmacokinetics in pregnancy
2023
Texas A&M University, College Station, USA(1)
The University of Texas Medical Branch at Galveston, Galveston, USA(2)
The University of Texas Medical Branch at Galveston, Galveston, USA(2)
Preterm birth rates and maternal and neonatal mortality remain important global health issues that require improved strategies for testing therapeutic agents during pregnancy. This study therefore investigated the utility of in silico simulation models and microfluidic organ-on-a-chip platforms to test potential drugs.
For this purpose, a feto-maternal multi-organ-on-a-chip (FMi-PLA-OOC) interface with microfluidic channels to maintain intercellular interactions between seven different cell types (fetal membrane-decidua-placenta) was developed. This platform enabled the study of drug pharmacokinetics in vitro. Pravastatin, a model drug known for its efficacy in reducing oxidative stress and inflammation during pregnancy and currently in clinical trials, was used to test its transfer rate across both feto-maternal interfaces. Additionally, mechanistically based simulation software (Gastroplus®) was employed to predict pravastatin pharmacokinetics in pregnant subjects based on validated non-pregnant drug data. The transfer of pravastatin by the FMi-PLA-OOC and the predicted pharmacokinetics in the in silico models were similar at approximately 18%.
The results of this study suggest that the FMi-PLA-OOC and In-silico models can serve as alternative methods to study the pharmacokinetics of drugs during pregnancy and provide valuable insights into drug transport and metabolism across the placenta and fetal membranes.
Microfluidic technology and simulation models in studying pharmacokinetics during pregnancy
Arum Han(1), Ramkumar Menon(2)
Added on: 09-20-2023
[1] https://www.frontiersin.org/articles/10.3389/fphar.2023.1241815/full
