ArticleClinical pharmacokinetics2020
Integration of Placental Transfer in a Fetal-Maternal Physiologically Based Pharmacokinetic Model to Characterize Acetaminophen Exposure and Metabolic Clearance in the Fetus.
Article in Clinical pharmacokinetics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 1 of them a synthesis that pooled it.
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Who cites it
35 citing papers in PubMed, 1 synthesis or guideline pooled it, 53 citations in OpenAlex.
- Evaluation of the evidence on acetaminophen use and neurodevelopmental disorders using the Navigation Guide methodology.Environmental health : a global access science source · 2025Pooled it
- PBPK Models for Fetal Drug Exposure: A Critical Assessment of Current Approaches and Regulatory Readiness.Journal of clinical pharmacology · 2026Review
- Beyond the Headlines: Examining the Evidence Around Acetaminophen and Autism Risk.The journal of pediatric pharmacology and therapeutics : JPPT : the official journal of PPAG · 2026Article
- Exposure to nitrosatable drugs during pregnancy and childhood cancer: A cohort study in Taiwan.International journal of cancer · 2026Article
- Simulation of Imatinib Pharmacokinetics in pregnant women with chronic myeloid leukemia in the third trimester.European journal of clinical pharmacology · 2026Article
- Sotalol Dose Optimization for Fetal Tachycardia: A Pregnancy Physiologically Based Pharmacokinetic Model Study.Prenatal diagnosis · 2026Article
- Exposure to Acetaminophen (Paracetamol) during Pregnancy and Childhood Cancer: A Population-Based Cohort Study in Taiwan.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2026Article
- The interaction between paracetamol and ethanol during the early development of zebrafish.Frontiers in pharmacology · 2026Article
- NAPQI is absent in the mouse brain after sub-hepatotoxic and hepatotoxic doses of acetaminophen.Toxicological sciences : an official journal of the Society of Toxicology · 2025Article
- Toward Precision Dosing of Lamotrigine During Pregnancy: Physiologically Based Pharmacokinetic Modeling and Simulation.CPT: pharmacometrics & systems pharmacology · 2025Article
- Umbilical cord blood gentamicin concentrations at delivery: placental physiology at work.Pediatric research · 2025Article
- Strategy advancements in placental pharmacokinetics: fromFrontiers in pharmacology · 2025Review
- Coupling Pre- and Postnatal Infant Exposures with Physiologically Based Pharmacokinetic Modeling to Predict Cumulative Maternal Levetiracetam Exposure During Breastfeeding.Clinical pharmacokinetics · 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
- Effects of Prenatal Paracetamol Exposure on the Development of Asthma and Wheezing in Childhood: A Systematic Review and Meta-Analysis.Journal of clinical medicine · 2023Review
- Drug exposure during pregnancy: Current understanding and approaches to measure maternal-fetal drug exposure.Frontiers in pharmacology · 2023Review
- Potential adverse actions of prenatal exposure of acetaminophen to offspring.Frontiers in pharmacology · 2023Review
- Application of Physiologically Based Pharmacokinetic Modeling to Predict Maternal Pharmacokinetics and Fetal Exposure to Oxcarbazepine.Pharmaceutics · 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
9 authors at 6 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND AND
objectiveAlthough acetaminophen is frequently used during pregnancy, little is known about fetal acetaminophen pharmacokinetics. Acetaminophen safety evaluation has typically focused on hepatotoxicity, while other events (fetal ductal closure/constriction) are also relevant. We aimed to develop a fetal-maternal physiologically based pharmacokinetic (PBPK) model (f-m PBPK) to quantitatively predict placental acetaminophen transfer, characterize fetal acetaminophen exposure, and quantify the contributions of specific clearance pathways in the term fetus.
methodsAn acetaminophen pregnancy PBPK model was extended with a compartment representing the fetal liver, which included maturation of relevant enzymes. Different approaches to describe placental transfer were evaluated (ex vivo cotyledon perfusion experiments, placental transfer prediction based on Caco-2 cell permeability or physicochemical properties [MoBi
resultsTested approaches to predict placental transfer showed comparable performance, although the ex vivo approach showed highest prediction accuracy. Acetaminophen exposure in maternal venous blood was similar to fetal venous umbilical cord blood. Prediction of fetal acetaminophen clearance indicated that the median molar dose fraction converted to acetaminophen-sulphate and N-acetyl-p-benzoquinone imine was 0.8% and 0.06%, respectively. The predicted mean acetaminophen concentration in the arterial umbilical cord blood was 3.6 mg/L.
conclusionThe median dose fraction of acetaminophen converted to its metabolites in the term fetus was predicted. The various placental transfer approaches supported the development of a generic f-m PBPK model incorporating in vivo placental drug transfer. The predicted arterial umbilical cord acetaminophen concentration was far below the suggested postnatal threshold (24.47 mg/L) for ductal closure.
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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.