Using PBPK modeling to supplement clinical data and support the safe and effective use of dolutegravir in pregnant and lactating women

The article titled “Using PBPK modeling to supplement clinical data and support the safe and effective use of dolutegravir in pregnant and lactating women,” authored by Jia Ning, Amita Pansari, Karen Rowland Yeo, Aki T. Heikkinen, Catriona Waitt, and Lisa M. Almond, discusses the application of physiologically-based pharmacokinetic (PBPK) modeling to optimize dolutegravir dosing for pregnant and lactating women. The PBPK model, validated with clinical data from various populations, predicts how different UGT1A1 genetic phenotypes affect drug exposure. Findings indicate that the standard dolutegravir dose (50 mg daily) is generally appropriate during late pregnancy, regardless of UGT1A1 phenotype. Additionally, while breastfed infants may experience higher exposure levels, these remain significantly lower than maternal levels, suggesting that dolutegravir is safe for use in breastfeeding women. This study emphasizes the importance of PBPK modeling in guiding safe medication practices in populations often excluded from clinical trials.