ArticleDrug metabolism and disposition: the biological fate of chemicals2021
Predicting Maternal-Fetal Disposition of Fentanyl Following Intravenous and Epidural Administration Using Physiologically Based Pharmacokinetic Modeling.
Article in Drug metabolism and disposition: the biological fate of chemicals, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
13 citing papers in PubMed, 22 citations in OpenAlex.
- Pharmacometric modeling of opioid disposition in pregnancy: a systematic review of PopPK and PBPK approaches, model limitations, and future directions.Frontiers in pharmacology · 2026Review
- Pharmacokinetics of CYP2C19- and CYP3A4-Metabolized Drugs in Cirrhosis Using a Whole-Body PBPK Approach.Pharmaceutics · 2025Article
- Fentanyl exposure during preconception and gestation permanently dysregulates endogenous opioid peptides and sympathoadrenal-medullary axis in the offspring.Clinical science (London, England : 1979) · 2025Article
- Prediction of Pharmacokinetics for CYP3A4-Metabolized Drugs in Pediatrics and Geriatrics Using Dynamic Age-Dependent Physiologically Based Pharmacokinetic Models.Pharmaceutics · 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
- Strategy advancements in placental pharmacokinetics: fromFrontiers in pharmacology · 2025Review
- Advances in animal models of prenatal opioid exposure.Trends in neurosciences · 2024Review
- Fetal bladder rupture after high-dose maternal opioid treatment: a case report.Case reports in perinatal medicine · 2024Article
- Application of a physiologically based pharmacokinetic model to predict isoniazid disposition during pregnancy.Clinical and translational science · 2023Article
- Evaluating the Pharmacokinetics of Fentanyl in the Brain Extracellular Fluid, Saliva, Urine, and Plasma of Newborns from Transplacental Exposure from Parturient Mothers Dosed with Epidural Fentanyl Utilizing PBPK Modeling.European journal of drug metabolism and pharmacokinetics · 2023Article
- Review
- Comparative Evaluation of Intrathecal Dexmedetomidine and Fentanyl as an Adjuvant for Combined Spinal-Epidural Analgesia for Labor.Anesthesia, essays and researchesArticle
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Fentanyl is an opioid analgesic used to treat obstetrical pain in parturient women through epidural or intravenous route, and unfortunately can also be abused by pregnant women. Fentanyl is known to cross the placental barrier, but how the route of administration and time after dosing affects maternal-fetal disposition kinetics at different stages of pregnancy is not well characterized. To address this knowledge gap, we developed a maternal-fetal physiologically based pharmacokinetic (mf-PBPK) model for fentanyl to evaluate the feasibility to predict the maternal and fetal plasma concentration-time profiles of fentanyl after various dosing regimens. As fentanyl is typically given via the epidural route to control labor pain, an epidural dosing site was developed using alfentanil as a reference drug and extrapolated to fentanyl. Fetal hepatic clearance of fentanyl was predicted from CYP3A7-mediated norfentanyl formation in fetal liver microsomes (intrinsic clearance = 0.20 ± 0.05 µl/min/mg protein). The developed mf-PBPK model successfully captured fentanyl maternal and umbilical cord concentrations after epidural dosing and was used to simulate the concentrations after intravenous dosing (in a drug abuse situation). The distribution kinetics of fentanyl were found to have a considerable impact on the time course of maternal:umbilical cord concentration ratio and on interpretation of observed data. The data show that mf-PBPK modeling can be used successfully to predict maternal disposition, transplacental distribution, and fetal exposure to fentanyl. SIGNIFICANCE STATEMENT: This study establishes the modeling framework for predicting the time course of maternal and fetal exposures of fentanyl opioids from mf-PBPK modeling. The model was validated based on fentanyl exposure data collected during labor and delivery after intravenous or epidural dosing. The results show that mf-PBPK modeling is a useful predictive tool for assessing fetal exposures to fentanyl opioid therapeutic regimens and potentially can be extended to other drugs of abuse.
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Registered trials
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