ArticleEuropean journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences2019
Using mechanistic physiologically-based pharmacokinetic models to assess prenatal drug exposure: Thalidomide versus efavirenz as case studies.
Article in European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
18 citing papers in PubMed, 26 citations in OpenAlex.
- Physiologically based pharmacokinetic modeling of long-acting extended-release naltrexone in pregnant women with opioid use disorder.CPT: pharmacometrics & systems pharmacology · 2024Trial
- Modelling the tail-phase pharmacokinetics of long-acting cabotegravir and rilpivirine from early pregnancy to postpartum at steady state.Journal of pharmacokinetics and pharmacodynamics · 2026Article
- PBPK Models for Fetal Drug Exposure: A Critical Assessment of Current Approaches and Regulatory Readiness.Journal of clinical pharmacology · 2026Review
- PKRxiv: A Best Practice Model for Advancing Pharmacoequity Through Open Pharmacokinetic Data Sharing.Clinical pharmacology and therapeutics · 2026Article
- Thalidomide-induced limb malformations: an update and reevaluation.Archives of toxicology · 2025Review
- Physiologically-based pharmacokinetic modelling of long-acting injectable cabotegravir and rilpivirine in pregnancy.British journal of clinical pharmacology · 2025Article
- Comparative modelling of foetal exposure to maternal long-acting injectable versus oral daily antipsychotics.npj women's health · 2025Article
- Strategy advancements in placental pharmacokinetics: fromFrontiers in pharmacology · 2025Review
- PBPK Modeling Approach to Predict the Behavior of Drugs Cleared by Metabolism in Pregnant Subjects and Fetuses.Pharmaceutics · 2024Article
- The Interplay of Permeability, Metabolism, Transporters, and Dosing in Determining the Dynamics of the Tissue/Plasma Partition Coefficient and Volume of Distribution-A Theoretical Investigation Using Permeability-Limited, Physiologically Based Pharmacokinetic Modeling.International journal of molecular sciences · 2023Article
- Considerations for the Use of Long-Acting and Extended-Release Agents During Pregnancy and Lactation.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2022Article
- Estimation of Fetal-to-Maternal Unbound Steady-State Plasma Concentration Ratio of P-Glycoprotein and/or Breast Cancer Resistance Protein Substrate Drugs Using a Maternal-Fetal Physiologically Based Pharmacokinetic Model.Drug metabolism and disposition: the biological fate of chemicals · 2022Article
- Optimizing Pharmacology Studies in Pregnant and Lactating Women Using Lessons From HIV: A Consensus Statement.Clinical pharmacology and therapeutics · 2021Article
- Maternal-Fetal Pharmacology of Drugs: A Review of Current Status of the Application of Physiologically Based Pharmacokinetic Models.Frontiers in pediatrics · 2021Review
- Mechanistic Coupling of a NovelFrontiers in pediatrics · 2021Article
- Mechanistic Modeling of Maternal Lymphoid and Fetal Plasma Antiretroviral Exposure During the Third Trimester.Frontiers in pediatrics · 2021Article
- Innovative Approaches for Pharmacology Studies in Pregnant and Lactating Women: A Viewpoint and Lessons from HIV.Clinical pharmacokinetics · 2020Article
- Drug dosing during pregnancy-opportunities for physiologically based pharmacokinetic models.Journal of pharmacokinetics and pharmacodynamics · 2020Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Maternofoetal physiologically-based pharmacokinetic models integrating multi-compartmental maternal and foetal units were developed using Simbiology® to estimate prenatal drug exposure. Processes governing drug disposition were described using differential equations with key system and drug-specific parameters. Transplacental drug transfer was modelled as bidirectional passive diffusion and benchmarked against those for thalidomide as a control. Model-predictions for pharmacokinetic parameters during pregnancy were within acceptable ranges for qualification (two-fold difference of clinically-observed values). Predicted foetal exposure to thalidomide was higher than efavirenz, with median (range) foetal-to-maternal plasma ratios of 4.55 (3.06-9.57) for 400 mg thalidomide versus 0.89 (0.73-1.05) for 400 mg efavirenz at third trimester. Model-predictions indicated foetal exposure consistently above 300% of maternal plasma concentration for thalidomide throughout pregnancy, while exposure to efavirenz increased from under 20% at second trimester to above 100% at third trimester. Further qualification of this approach as a tool in evaluating drug exposure and safety during pregnancy is warranted.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.