Pharmacokinetics of Medications in Pregnancy

Pregnancy induces profound anatomical and physiological adaptations that alter the absorption, distribution, metabolism and excretion of many medications. Expanded maternal blood volume and cardiac output increase distribution volumes, while decreased plasma protein concentrations enhance the free fraction of drugs. Gastrointestinal motility may be delayed, affecting oral absorption rates, and changes in hepatic enzyme activity—both induction and inhibition—modify metabolic clearance. Renal blood flow and glomerular filtration rate rise markedly, accelerating elimination of renally cleared compounds. Collectively, these processes can lead to reduced drug exposure at standard doses, with implications for therapeutic efficacy and fetal safety. A nuanced understanding of these dynamics is crucial to optimise dosing regimens, minimise adverse outcomes and ensure effective maternal treatment during gestation.

Research from Nature Portfolio

A large prospective birth cohort has established a comprehensive biospecimen repository alongside detailed records of maternal drug exposure during early gestation. In over 110,000 women, approximately one in three received at least one medication in the first trimester, with synthetic progestogens among the most frequently prescribed agents. Analysis revealed associations between early progestogen use and increased risks of stillbirth, preterm delivery and congenital anomalies, though causality remains to be determined. Ongoing follow-up and deeper molecular profiling of maternal and cord blood samples aim to clarify dose–response relationships and to identify biomarkers predictive of both maternal pharmacokinetics and fetal outcomes.

Pharmacokinetics of Medications in Pregnancy publication trend

The graph below shows the total number of articles in pharmacokinetics of medications in pregnancy across all publications each year (not limited to Nature Index journals).

Technical terms

Pharmacokinetics: The study of how drugs are absorbed, distributed, metabolised and excreted in the body.

Absorption: The process by which a drug enters the bloodstream from its site of administration.

Distribution: The dispersion of a drug throughout the fluids and tissues of the body.

Metabolism: The chemical transformation of a drug, primarily in the liver, into metabolites.

Excretion: The removal of a drug and its metabolites from the body, often via urine or bile.

Clearance: The volume of plasma from which a drug is completely removed per unit time.

Bioavailability: The proportion of an administered dose that reaches systemic circulation unchanged.

Polypharmacy: The concurrent use of multiple medications by a single patient.

Teratogenic: Capable of causing developmental malformations in an embryo or foetus.

References

1. The maternal drug exposure birth cohort (DEBC) in China. Nature Communications (2024).
2. Analysis of risk evaluation and mitigation strategies for teratogenic drugs: Variation in primary and secondary prevention measures. PLOS Medicine (2023).
3. Polypharmacy during pregnancy and associated risk factors: a retrospective analysis of 577 medication exposures among 1.5 million pregnancies in the UK, 2000-2019. BMC Medicine (2023).
4. Pregnancy-Associated Changes in Pharmacokinetics: A Systematic Review. PLOS Medicine (2016).
5. Physiologic and pharmacokinetic changes in pregnancy. Frontiers in Pharmacology (2014).