ArticleEuropean journal of drug metabolism and pharmacokinetics2023
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.
Article in European journal of drug metabolism and pharmacokinetics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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5 citing papers in PubMed, 9 citations in OpenAlex.
- Plasma and colostrum concentrations of fentanyl in clinical practice: Intravenous versus epidural administration for labor analgesia.Acta obstetricia et gynecologica Scandinavica · 2026Article
- Pharmacometric modeling of opioid disposition in pregnancy: a systematic review of PopPK and PBPK approaches, model limitations, and future directions.Frontiers in pharmacology · 2026Review
- QSAR-based physiologically based pharmacokinetic (PBPK) modeling for 34 fentanyl analogs: model validation, human pharmacokinetic prediction and abuse risk insights.Frontiers in pharmacology · 2025Article
- The Effect of Inflammatory Bowel Disease and Irritable Bowel Syndrome on Pravastatin Oral Bioavailability: In vivo and in silico evaluation using bottom-up wbPBPK modeling.AAPS PharmSciTech · 2024Article
- 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
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1 author at 1 institution in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND AND
objectiveFentanyl can mitigate the mother and newborn complications resulting from labor pain. However, fentanyl shows a narrow therapeutic index between its respiratory depressive and analgesic effects. Thus, prenatally acquired high fentanyl levels in the newborn brain extracellular fluid (bECF) may induce respiratory depression which requires therapeutic drug monitoring (TDM). TDM using saliva and urine in newborns can reduce the possibility of infections and distress associated with TDM using blood. The objective of this study was to develop a physiologically based pharmacokinetic (PBPK) model to predict fentanyl concentrations in different newborn tissues due to intrauterine exposure.
methodsA fentanyl PBPK model in adults after intravenous and epidural administration was built, validated, and scaled to pregnancy and newborn populations. The dose that the newborn received transplacentally at birth was calculated using the pregnancy model. Then, the newborn bECF, saliva, plasma, and urine concentrations after such a dose were predicted using the newborn PBPK model.
resultsAfter a maternal epidural dose of fentanyl 245 µg, the predicted newborn plasma and bECF levels were below the toxicity thresholds. Furthermore, the salivary threshold levels in newborns for fentanyl analgesic and respiratory depression effects were estimated to be 0.39 and 14.7-18.2 ng/ml, respectively.
conclusionThe salivary TDM of fentanyl in newborns can be useful in newborns exposed to intrauterine exposure from parturient females dosed with epidural fentanyl. However, newborn-specific values of µ-opioid receptors IC
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