Over two-thirds of women receive prescription drugs while pregnant. These may be for pre-existing medical conditions or symptoms arising as a result of pregnancy. Most often, the advice is to avoid the use of medicines during pregnancy and breastfeeding.
Changes in maternal physiology as a result of pregnancy may affect the disposition of any administered drug. For example, blood flow to the uterus increases 10-fold from 50 to 500 mL/min at term. Furthermore, small-molecular-weight and lipophilic drugs readily cross the placenta. The foetus and the amniotic fluid can act as additional compartments, leading to increased drug accumulation and an apparent increase in volume of distribution of certain drugs. All these adaptations can influence the dose required for therapeutic effect. A more detailed account of drug disposition in pregnancy is provided in the review paper by Feghali.
Nevertheless, treatment dosing strategies in pregnancy are largely based upon studies in healthy male volunteers and non-pregnant women. The recent announcement by the MHRA that they are partnering with the Bill and Melinda Gates Foundation to look at more effective use of medicines during pregnancy is to be welcomed. This initiative is part of the MHRA’s broader programme of work that is contributing to World Patient Safety Day (17 September). At the core of this project is the investigation of the influence of the physiological changes that occur during pregnancy on drug disposition. The impact will be assessed using physiologically-based pharmacokinetic modelling. Output from this approach will be used to improve dose selection in this neglected population, in addition to improving the benefit-risk assessment of medicines in this field. I look forward to reading the results, from this much needed project, in the published literature.
Feghali M, Venkataramanan R, Caritis S. Pharmacokinetics of drugs in pregnancy. Semin Perinatol. 2015;39(7):512-519.