ArticleDrug metabolism and disposition: the biological fate of chemicals2017
Development of a Novel Maternal-Fetal Physiologically Based Pharmacokinetic Model I: Insights into Factors that Determine Fetal Drug Exposure through Simulations and Sensitivity Analyses.
Article in Drug metabolism and disposition: the biological fate of chemicals, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers, 1 of them a synthesis that pooled it.
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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
57 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Fetal Physiologically Based Pharmacokinetic Models: Systems Information on the Growth and Composition of Fetal Organs.Clinical pharmacokinetics · 2019Pooled it
- Physiologically based pharmacokinetic modeling of long-acting extended-release naltrexone in pregnant women with opioid use disorder.CPT: pharmacometrics & systems pharmacology · 2024Trial
- Exclusion by Design: Regulatory Reform and Evolving Frameworks for Clinical Trials in Pregnancy.Paediatric drugs · 2026Review
- PBPK Models for Fetal Drug Exposure: A Critical Assessment of Current Approaches and Regulatory Readiness.Journal of clinical pharmacology · 2026Review
- Female Reproductive Tract Organ-on-Chips: Modeling Barrier Function and Drug Transport.Pharmaceutics · 2026Review
- Comparison of physiologically based pharmacokinetic modeling platforms for developmental neurotoxicity in vitro to in vivo extrapolation.Toxicological sciences : an official journal of the Society of Toxicology · 2026Article
- Predicting Maternal and Fetal Exposures of Elexacaftor-Tezacaftor-Ivacaftor during Pregnancy through Physiologically Based Pharmacokinetic Models.Clinical pharmacology and therapeutics · 2025Article
- The impact of prenatal amoxicillin exposure at different doses, stages, and courses on offspring ovarian development.Molecular medicine (Cambridge, Mass.) · 2025Article
- Rat PermQ: A permeability- and perfusion-based physiologically based pharmacokinetic model for improved prediction of drug concentration-time profiles in rat.Drug metabolism and disposition: the biological fate of chemicals · 2025Article
- Quantification and prediction of human fetal (-)-ΔNature communications · 2025Article
- Physiologically based pharmacokinetic modeling of small molecules: How much progress have we made?Drug metabolism and disposition: the biological fate of chemicals · 2025Review
- 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
- Advancing understanding of human variability through toxicokinetic modeling, in vitro-in vivo extrapolation, and new approach methodologies.Human genomics · 2024Review
- Using PBPK modeling to supplement clinical data and support the safe and effective use of dolutegravir in pregnant and lactating women.CPT: pharmacometrics & systems pharmacology · 2024Article
- PBPK Modeling Approach to Predict the Behavior of Drugs Cleared by Metabolism in Pregnant Subjects and Fetuses.Pharmaceutics · 2024Article
- Development of a Generic Fetal Physiologically Based Pharmacokinetic Model and Prediction of Human Maternal and Fetal Organ Concentrations of Cefuroxime.Clinical pharmacokinetics · 2024Article
- Drug exposure during pregnancy: Current understanding and approaches to measure maternal-fetal drug exposure.Frontiers in pharmacology · 2023Review
- Evaluation of a rapid, generic human gestational dose model.Reproductive toxicology (Elmsford, N.Y.) · 2022Article
- An update on placental drug transport and its relevance to fetal drug exposure.Medical review (2021) · 2022Review
Corrections and comments
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Authors and funding
6 authors.
Funding
Abstract
Determining fetal drug exposure (except at the time of birth) is not possible for both logistical and ethical reasons. Therefore, we developed a novel maternal-fetal physiologically based pharmacokinetic (m-f-PBPK) model to predict fetal exposure to drugs and populated this model with gestational age-dependent changes in maternal-fetal physiology. Then, we used this m-f-PBPK to: 1) perform a series of sensitivity analyses to quantitatively demonstrate the impact of fetoplacental metabolism and placental transport on fetal drug exposure for various drug-dosing regimens administered to the mother; 2) predict the impact of gestational age on fetal drug exposure; and 3) demonstrate that a single umbilical venous (UV)/maternal plasma (MP) ratio (even after multiple-dose oral administration to steady state) does not necessarily reflect fetal drug exposure. In addition, we verified the implementation of this m-f-PBPK model by comparing the predicted UV/MP and fetal/MP AUC ratios with those predicted at steady state after an intravenous infusion. Our simulations yielded novel insights into the quantitative contribution of fetoplacental metabolism and/or placental transport on gestational age-dependent fetal drug exposure. Through sensitivity analyses, we demonstrated that the UV/MP ratio does not measure the extent of fetal drug exposure unless obtained at steady state after an intravenous infusion or when there is little or no fluctuation in MP drug concentrations after multiple-dose oral administration. The proposed m-f-PBPK model can be used to predict fetal exposure to drugs across gestational ages and therefore provide the necessary information to assess the risk of drug toxicity to the fetus.
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