Strategy Advancements in Placental Pharmacokinetics: From In Vitro Experiments to In Silico Prediction

Zhimin Li¹Yue Wu¹Siyu Zeng¹Fei Wang¹JIAO ZHANG²Shiran Li¹Yong Yang^1*Yujie Yang^3*

• ¹Department of Pharmacy, Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of China, chengdu, China
• ²Chongqing Red Cross Hospital, Chongqing, China
• ³Chengdu Third People's Hospital, Chengdu, China

Background: The placental barrier is a critical interface regulating drug transport between maternal and foetal circulation and an important component in assessing foetal drug exposure risk. Since pregnant women are often excluded from clinical trials, pharmacokinetic (PK) data on placental drug transport remain limited. Currently, in vitro experiments and in silico simulation strategies are the primary and effective means for understanding drug transport across the placenta. Method: Various in vitro experimental methods, including cell monolayer models, ex vivo placental perfusion, and organ-on-a-chip platforms, as well as model-based computational simulations, were systematically reviewed. The advantages, limitations, and potential future applications of these methods were evaluated. Result: A total of 7 studies using cell models, 28 employing ex vivo perfusion, 6 utilizing placental-on-a-chip technology, and 39 focusing on in silico simulations were identified, involving 8, 34, 5, and 42 drugs, respectively. Antiviral agents, antibiotics, and opioids were the most frequently investigated. Overall, in silico simulations informed by in vitro data as baseline parameters and constraints demonstrated higher predictive accuracy. Integrating multi-model data was shown to be a reliable strategy for improving the precision of placental pharmacokinetic studies. Conclusion:This review highlights the current strategies in placental pharmacokinetic research and supports safer drug use during pregnancy. Multi-model data integration is essential for developing reliable and quantitative foetal drug exposure assessment frameworks, addressing data gaps caused by the exclusion of pregnant women from clinical trials.