Karen Yeo, PhD, on leveraging PBPK modeling for drug dosing in pregnancy

Karen Yeo, PhD, Senior vice president, Client & Regulatory Strategy, Certara UK, joined Contemporary OB/GYN to discuss how to close this gap in evidence-based dosing during pregnancy, via physiologically based pharmacokinetic (PBPK) modeling. The modeling uses virtual populations to predict drug exposure to provide a quantitative framework for administering medications to pregnant and breastfeeding patients.

The PBPK approach utilizes in vitro data generated during drug development to create virtual populations that account for the dynamic physiological changes occurring across all 3 trimesters. Yeo noted that her team has helped pharmaceutical companies develop between 100 and 200 PBPK models to predict pregnancy outcomes. These models serve as a digital comparison to traditional clinical trials, scaling data to predict drug exposures in plasma with high precision.

“We have been responsible for helping pharmaceutical companies develop between 100 and 200 PBPK models, and we can use these models to predict outcomes in pregnancy,” Yeo explained. Over the last decade, this focus has shifted toward the global health space, particularly for patients in Sub-Saharan Africa who require specialized dosing support during pregnancy and lactation.

Empowering clinicians through global education

A significant barrier to the adoption of these quantitative approaches is the perception of modeling as a "black box," as Yeo stated. To address this, Yeo has spent the last 5 years hosting workshops for non-modelers, including OB/GYNs, pharmacists, and healthcare practitioners. These efforts have spanned the United States, Uganda, and Thailand, with upcoming initiatives in South America.

“We are trying to explain the PBPK approaches so that it becomes less of a 'black box' and more of an approach with which they are familiar,” Yeo said.

A shift toward informed, patient-centered dosing

The evolution of PBPK modeling is not just technical, but it is increasingly personal. Yeo emphasized that the focus over the last 5 years has shifted toward involving pregnant patients directly in their dosing decisions. This collaborative approach ensures that women are informed participants in their treatment plans.

“The approach over the last 5 years has focused much more on the patient... being involved in their dosing decisions and informed decision-making with clinicians,” Yeo concluded.