During pregnancy, a woman’s body undergoes major physiological changes that can profoundly alter how drugs are absorbed, distributed, metabolized, and excreted. The effects vary by drug: increased plasma volume and body fat can dilute hydrophilic and lipophilic medications differently, liver enzyme activity may speed up or slow metabolism, and higher renal clearance can accelerate elimination of renally excreted drugs.

Placental transfer is another key consideration, determining how much drug reaches the foetus. Transfer depends on drug properties—molecular weight, lipophilicity, protein binding, and ionization—and the timing of exposure, which shapes whether foetal effects are therapeutic, developmental, or potentially harmful. Together, these factors guide whether a medicine should be used in pregnancy and whether maternal or foetal dosing adjustments are needed.

Thus, a dose that works in a non-pregnant adult may be ineffective—or unsafe—during pregnancy. Without adjustment, therapy risks under-treating the mother or exposing the foetus to excessive drug levels. Clinicians must consider altered pharmacokinetics, placental transfer, and gestational timing to ensure safe and effective treatment.

Despite the widespread use of medication during pregnancy, pregnancy-specific clinical data regarding dosing are scarce. This lack of evidence leaves a gap in our understanding of how drugs behave in pregnant patients. Resulting that most medicines prescribed in pregnancy are often based non-pregnant adult data, which in turn can cause uncertainty about efficacy, safety, and drug interactions.

Absorption

During pregnancy, stomach acidity decreases and the production of the hormone progesterone increases. Lower stomach acidity reduces the absorption of basic drugs (drugs with a high pH) while it increases the absorption of acidic drugs (drugs with a lower pH). Progesterone causes smooth muscle cells in the gastrointestinal tract to relax. This slows down gastric emptying and gut movements. Consequently, drugs are absorbed more slowly. On the other hand, the cardiac output (the amount of blood the heart pumps through the body per minute) increases during pregnancy. Because of this, more blood is pumped towards the intestines. This, in turn, enhances the absorption of drugs. In addition, many women experience nausea and vomiting in early pregnancy. This may decrease the amount of drug available for absorption, especially following oral intake.

Overall, the effect of pregnancy on absorption is drug-specific. However, taken together, the effects of pregnancy on drug absorption are likely to be minimal as pregnancy-induced changes in the gastrointestinal system that reduce drug absorption are compensated by the increase in cardiac output.

Distribution

The amount of blood, body water and body fat significantly increases during pregnancy. This causes drugs to spread differently in the body and causes changes in the volume of distribution of a drug. The volume of distribution of a drug is a measure of how extensively it spreads across the body. The a drug’s volume of distribution depends on its physical and chemical characteristics. Drugs can either be lipophilic (repelled by water and attracted to fat) or hydrophilic (favouring water and repelled by fat). With more body water in pregnancy, hydrophilic drugs dilute into a larger space, often producing lower peak blood concentrations and sometimes a longer half-life. Similarly, increased fat stores can expand the Vd for lipophilic drugs.

Also, changes in plasma proteins during pregnancy can impact drug distribution. Due to the increasing blood volume in pregnancy, the concentration of proteins circulating in the bloodstream decreases. An example of a plasma protein that shows a decrease in concentration during pregnancy is albumin. With fewer binding proteins, a larger proportion of the drug remains unbound. These changes can impact the volume of distribution and potentially the (pharmacodynamic) effects of a drug, especially if the unbound drug distributes poorly into tissues or is cleared slowly.

Overall, due to a higher volume of fluids in the body, pregnancy often leads to lower peak concentrations of drugs in the bloodstream. This may lead to lower efficacy for certain drugs.      

Metabolism

Drug breakdown (metabolism) enables elimination via urine or faeces and is carried out primarily by liver cytochrome P450 (CYP) enzymes, though other enzymes can also be involved. Pregnancy hormones, such as progesterone and oestradiol, change the abundance and activity of these enzymes , some increase, others decrease. Liver blood flow also rises, further influencing metabolism. As a result, some drugs are broken down faster, lowering plasma levels, while others are metabolized more slowly, increasing plasma levels. The effect depends on the specific enzymes involved for each drug.

Elimination

Alongside drug metabolism by liver enzymes, the kidneys play an important role in removing drugs from the body. Because of an increased cardiac output in pregnancy, there is an increased blood flow to the kidneys. This change starts in the second trimester and continues during the third trimester of pregnancy. In addition, due to the increase of unbound drug in the bloodstream during pregnancy, drugs that are filtered by the kidneys are removed from the body more quickly during pregnancy. Faster renal filtration results in an increased drug clearance. On top of renal filtration, the kidneys contain small channels (‘tubules’) that can reabsorb drugs from urine as well as secrete drugs into urine. Renal absorption and secretion are also influenced by hormonal changes as part of pregnancy. This may impact the speed of drug removal from the body.

Overall, drugs tend to be removed faster from the body during pregnancy. This is mainly a result of increased renal filtration. These changes can result in shorter durations of therapeutic levels of the drug in the body during pregnancy.

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. 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.

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. 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.

From the simulation results, a dosing regimen is selected that meets the pharmacokinetic target for most of the virtual population while avoiding levels that are too low (risking treatment failure) or too high (risking toxicity). Any model-informed dosing recommendation is reviewed by clinicians, pharmacists, and other experts to ensure it is safe, practical, and supported by other evidence. Considerations include:

•    How different the dose is from current practice

•    Whether the regimen is feasible in real-world care

•    How to monitor drug levels or clinical response if needed

•    The consequences if predictions are wrong

Whether you’re ready to adjust dosing today or you want to explore the science behind the recommendations, there are several ways to engage with model-informed dosing (MID) for pregnancy.

• Medication specific details: Read the summary or full Dosing recommendation Document per each endorsed medication
• PBPK guidance: link to PBKP learning tools?
• Model-informed Dosing: link to Modelers webpage?
• Scientific literature: browse through all our peer-reviewed publications

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