Using mechanistic physiologically-based pharmacokinetic models to assess prenatal drug exposure: Thalidomide versus efavirenz as case studies.

ABSTRACT: Maternofoetal physiologically-based pharmacokinetic models integrating multi-compartmental maternal and foetal units were developed using Simbiology® to estimate prenatal drug exposure. Processes governing drug disposition were described using differential equations with key system and drug-specific parameters. Transplacental drug transfer was modelled as bidirectional passive diffusion and benchmarked against those for thalidomide as a control. Model-predictions for pharmacokinetic parameters during pregnancy were within acceptable ranges for qualification (two-fold difference of clinically-observed values). Predicted foetal exposure to thalidomide was higher than efavirenz, with median (range) foetal-to-maternal plasma ratios of 4.55 (3.06-9.57) for 400 mg thalidomide versus 0.89 (0.73-1

SUBMITTER: Atoyebi SA 

PROVIDER: S-EPMC6853277 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature