We are working with the Bill and Melinda Gates Foundation on an exciting pharmacokinetics (PK) project which should lead to better informed use of medicine during pregnancy and the development of medicines which are safer for use in pregnancy.
Our aim is to improve the knowledge of medicines used during pregnancy, based on changes in blood concentrations, and to evaluate existing mathematical physiologically-based pharmacokinetic (PBPK) models for their potential to support dosing in pregnant women.
Use of medicines in pregnancy
Only a small number of medicines are specifically licensed for use in pregnant women and it is generally recommended to avoid use of medicines during pregnancy and breastfeeding. However, more than half of all pregnant women use at least one medicinal product during their pregnancy and there are some conditions for which treatment is essential. These include depression, diabetes, epilepsy, cardiovascular conditions, or treatment with antiviral agents. Other medicines may be required for specific conditions like pre-eclampsia that may develop in pregnancy.
Despite this, the optimal formulation and dosage of most medications in pregnant women has largely not been investigated. Moreover, major physiological, anatomical and biochemical changes occur in the mother’s body during pregnancy to support the development of the foetus. These factors may have an effect on the absorption (how a medicine is taken up), distribution (where it is accumulated), metabolism (how it is broken down) and elimination (how it is removed from the body).
PBPK modelling
PBPK modelling uses a mathematical approach to develop an understanding of how drug distribution and elimination occurs in the body and how drug levels in the blood and other organs can be influenced by the changes in physiology. Some PBPK models already exist for pregnancy but current information is limited. In this project we will investigate how well the models predict PK exposure of drugs in pregnant women and their potential to select the dose in pregnant women when clinical data is sparse or absent. We will also investigate how these models can be used to support the design and conduct of clinical research in this neglected population.
With input from UK clinical experts, we have identified drugs commonly used in pregnancy, for which we aim to investigate the impact of pregnancy on their PK by using available information and PBPK modelling. We aim to facilitate the provision of the best quantitative PK information to support dose selection for these drugs and to inform an improved benefit-risk assessment of the medicines in pregnancy.
Information will be shared with healthcare professionals and training will be provided on how to use the models as an optional extra to the MHRA training in PK in pregnancy for healthcare professionals.
Further information on this project is available in this press release.
Get in touch
We would be very interested to hear from you if you have the opportunity to provide PK data on any medicine commonly used by pregnant women. Please email PK.Pregnancy.Workshop@mhra.gov.uk.