Physiologically-based pharmacokinetic (PBPK) modeling allows the changes in drug exposure that occur during the various stages of pregnancy to be simulated, guiding dose adjustment decisions and increasing safety for this vulnerable group of patients.
For ethical reasons, pregnant women are actively excluded from drug studies. As a result, there is a lack of clinical data on how the well-documented physiological and biochemical changes that occur during pregnancy will affect maternal drug exposure. Clinicians are faced with decisions to prescribe “off-label” drugs that are unlicensed for pregnant women, often scaling doses from the recommendations set for men or non-pregnant women. This can lead to under-dosing, with lack of therapeutic effect, or over-dosing, with potential toxicity that endangers both mother and developing fetus.
Recent moves by the US FDA and European Medicines Agency are addressing this issue by requiring that post-marketing studies be conducted into the effects of drugs in pregnancy where there is a high likelihood of use in women of child-bearing age. The challenge for pharmaceutical companies is not only to determine appropriate initial dosing levels—which will vary depending on the stage of pregnancy—but also account for the time-related changes in drug exposure that may occur over an extended study period. As the physiological and biological changes that occur during pregnancy are well-studied, building physiologically-based models to study pharmacokinetics is an intuitive solution.