Year: 2016
Type: dissertation
Abstract: Medication use during pregnancy requires a balance between treating a condition in the mother, and minimizing potential risks in the fetus. In recent years, it has been estimated that between 50 and 70% of pregnant women in North America will take at least one prescription medication during their pregnancy. The decision to begin or continue treatment during pregnancy relies heavily on evaluating the risk-benefit ratio, and an important determinant in this risk assessment is estimating fetal drug exposure. The use of medications in pregnant women can be especially challenging, as there is very limited safety data in pregnancy. Recently, novel oral anticoagulants have been developed and approved for clinical use. However, the information regarding their fetal safety and placental transfer in humans is unknown. We used the ex vivo placenta perfusion model to investigate anticoagulant (dabigatran, rivaroxaban, apixaban) transfer across the human placenta. Rivaroxaban and apixaban rapidly crossed the term human placenta, while dabigatran crossed the placenta to a lesser extent. The placenta perfusion results were adjusted to account for protein binding and pH differences between the mother and fetus. We also developed a pharmacokinetic model that adequately described the transplacental transfer of anticoagulants by using data from our experiments. While the placenta perfusion model can be technically challenging, its results strongly correlate with in vivo placental transfer data. By evaluating the success rate of the perfusion model in our laboratory, we determined that establishing the fetal circulation is an important stage of the protocol. This information can be used to create a focused training program to help increase the overall success rate of this model and productivity of the lab. Drug use in pregnancy is multifactorial, and placental transfer data is important in assessing which drugs can be used to treat the mother while protecting the unborn.
Source: TSpace (University of Toronto)
Author: Priya Bapat
Language: English
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2609599358