Model-informed dosing in pregnancy
Placental transfer
During pregnancy, alongside changes in a woman’s body, drug pharmacokinetics are affected by the growth of the placenta and the foetus. In pregnancy, a connection is established between the mother’s bloodstream and the foetus’ bloodstream through the placenta. The placenta acts both as a gate and a barrier for the transport of substances between mother and foetus, as illustrated in figure 3. Examples of substances that can cross the placenta are nutrients, oxygen, antibodies, and waste products. Most drugs can also cross the placenta, potentially reaching the foetus. The degree of placental transfer of a drug depends on drug characteristics such as molecular size and its lipophilicity (4-12).
Figure 3. schematic overview of the connection between maternal and foetus’ bloodstream. Illustration adapted from: Biorender.
The placental transfer of drugs is a key consideration in the context of pharmacotherapy during pregnancy for several reasons. First, some drugs are administered to a pregnant woman with the intention of treating the foetus. For instance, antibiotics can be used to treat infections of the uterus, thereby protecting the child. In these cases, placental transfer from the mother to the foetus is a prerequisite for the drug to have the desired effect. From a pharmacokinetic stance, placental transfer and metabolism, along with foetal metabolism (the breakdown of drugs in the foetus’s body) influences the amount of drug a mother and her foetus(es) are exposed to. This can affect the effectiveness of a drug. Lastly, some drugs may influence the development of the foetus, potentially causing adverse effects (4-12).
Overall, The extent of placental drug transfer and the desired and unwanted effects of the drug on the foetus determine whether a drug can be used or not during pregnancy.