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Determination of the Transport Rate of Xenobiotics and Nanomaterials Across the Placenta using the ex vivo Human Placental Perfusion Model
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Forecasting Fetal Buprenorphine Exposure through Maternal-Fetal Physiologically Based Pharmacokinetic Modeling
Matthijs W van Hoogdalem1,2, Ryota Tanaka1, Khaled Abduljalil3
1Division of Translational and Clinical Pharmacology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
Pharmaceutics
|March 28, 2024
Summary
This study developed a maternal-fetal pharmacokinetic model to predict fetal buprenorphine exposure. This model can help tailor doses to reduce neonatal opioid withdrawal syndrome (NOWS) severity.
Area of Science:
- Pharmacology
- Pharmacokinetics
- Maternal-Fetal Medicine
Background:
- Buprenorphine crosses the placenta, potentially increasing neonatal opioid withdrawal syndrome (NOWS) severity with higher prenatal exposure.
- Optimizing buprenorphine dosing requires understanding fetal exposure levels and predicting NOWS severity.
Purpose of the Study:
- To develop a maternal-fetal physiologically based pharmacokinetic (PBPK) model for sublingual buprenorphine.
- To predict fetal buprenorphine exposure and its correlation with NOWS severity.
Main Methods:
- A maternal-fetal PBPK model was created using Simcyp (v21.0) to simulate buprenorphine transplacental passage.
- The model incorporated pregnancy-induced changes in maternal metabolism and transmucosal absorption.
- Model predictions were validated against maternal pharmacokinetic data and umbilical cord blood concentrations.
Main Results:
- Maternal buprenorphine pharmacokinetics were accurately predicted during the second and third trimesters and postpartum.
- Predicted umbilical cord blood concentrations closely matched observed values (geometric mean ratio 1.15), with 95.2% within a 2-fold error.
- The model adequately predicted buprenorphine concentrations in both maternal and fetal compartments.
Conclusions:
- The developed maternal-fetal PBPK model accurately forecasts fetal buprenorphine exposure.
- This tool can inform personalized buprenorphine dosing strategies to mitigate NOWS.
- Further investigation into the correlation between predicted fetal exposure and NOWS severity is warranted.
Keywords:
buprenorphinematernal–fetalneonatal opioid withdrawal syndromeopioid use disorderphysiologically based pharmacokinetic modelingMore Related Videos
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