ArticleClinical pharmacokinetics2017
A Physiologically-Based Pharmacokinetic Model to Predict Human Fetal Exposure for a Drug Metabolized by Several CYP450 Pathways.
Article in Clinical pharmacokinetics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
35 citing papers in PubMed, 58 citations in OpenAlex.
- Physiologically-based pharmacokinetic modelling of uridine 5'-diphosphoglucorosultransferase (UGT) substrate drugs in pregnant women.British journal of clinical pharmacology · 2026Article
- PBPK Models for Fetal Drug Exposure: A Critical Assessment of Current Approaches and Regulatory Readiness.Journal of clinical pharmacology · 2026Review
- Placenta models for HIV-1-ART-nicotine comorbidity research: advances and remaining challenges.Cell death discovery · 2026Review
- Application of Physiologically Based Pharmacokinetic Modeling in the Research of Anti-HIV Drugs.Current drug metabolism · 2025Review
- Strategy advancements in placental pharmacokinetics: fromFrontiers in pharmacology · 2025Review
- Physiologically Based Pharmacokinetic Modeling in Pregnancy, during Lactation and in Neonates: Achievements, Challenges and Future Directions.Pharmaceutics · 2024Article
- PBPK Modeling Approach to Predict the Behavior of Drugs Cleared by Metabolism in Pregnant Subjects and Fetuses.Pharmaceutics · 2024Article
- Assessment of rehabilitation treatment for patients with acute poisoning-induced toxic encephalopathy.World journal of emergency medicine · 2024Article
- Drug exposure during pregnancy: Current understanding and approaches to measure maternal-fetal drug exposure.Frontiers in pharmacology · 2023Review
- Prediction of Maternal and Fetal Doravirine Exposure by Integrating Physiologically Based Pharmacokinetic Modeling and Human Placenta Perfusion Experiments.Clinical pharmacokinetics · 2022Article
- Non-clinical considerations for supporting accelerated inclusion of pregnant women in pre-licensure clinical trials with anti-HIV agents.Journal of the International AIDS Society · 2022Article
- Prediction of Maternal and Fetal Acyclovir, Emtricitabine, Lamivudine, and Metformin Concentrations during Pregnancy Using a Physiologically Based Pharmacokinetic Modeling Approach.Clinical pharmacokinetics · 2022Article
- Re-orienting anti-malarial drug development to better serve pregnant women.Malaria journal · 2022Article
- Estimating fetal exposure to the P-gp substrates, corticosteroids, by PBPK modeling to inform prevention of neonatal respiratory distress syndrome.CPT: pharmacometrics & systems pharmacology · 2021Article
- The Role of the 3Rs for Understanding and Modeling the Human Placenta.Journal of clinical medicine · 2021Review
- PBPK Modeling Approach to Predict the Behavior of Drugs Cleared by Kidney in Pregnant Subjects and Fetus.The AAPS journal · 2021Article
- Mechanistic Modeling of Maternal Lymphoid and Fetal Plasma Antiretroviral Exposure During the Third Trimester.Frontiers in pediatrics · 2021Article
- Mechanistic Coupling of a NovelFrontiers in pediatrics · 2021Article
- Maternal-Fetal Pharmacology of Drugs: A Review of Current Status of the Application of Physiologically Based Pharmacokinetic Models.Frontiers in pediatrics · 2021Review
- Drug dosing during pregnancy-opportunities for physiologically based pharmacokinetic models.Journal of pharmacokinetics and pharmacodynamics · 2020Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundPregnant women and their fetuses are exposed to numerous drugs; however, they are orphan populations with respect to the safety and efficacy of drugs. Therefore, the prediction of maternal and fetal drug exposure prior to administration would be highly useful.
methodsA physiologically-based pharmacokinetic (PBPK) model for nevirapine, which is metabolized by the cytochrome P450 (CYP) 3A4, 2B6 and 2D6 pathways, was developed to predict maternal and fetal pharmacokinetics (PK). The model was developed in both non-pregnant and pregnant women, and all physiological and enzymatic changes that could impact nevirapine PK were taken into account. Transplacental parameters estimated from ex vivo human placenta perfusion experiments were included in this PBPK model. To validate the model, observed maternal and cord blood concentrations were compared with predicted concentrations, and the impact of fetal clearance on fetal PK was investigated.
resultsBy implementing physiological changes, including CYP3A4, 2D6 and 2B6 inductions, we predicted a clearance increase of 21 % in late pregnancy. The PBPK model successfully predicted the disposition for both non-pregnant and pregnant populations. Parameters obtained from the ex vivo experiments allowed the prediction of nevirapine concentrations that matched observed cord blood concentrations. The fetal-to-maternal area under the curve ratio (0-24 h interval) was 0.77, and fetal metabolism had no significant effect on fetal PK.
conclusionsThe PBPK approach is a useful tool for quantifying a priori the drug exposure of metabolized drugs during pregnancy, and can be applied to evaluate alternative dosing regimens to optimize drug therapy. This approach, including ex vivo human placental perfusion parameters, is a promising approach for predicting human fetal exposure.
Indexed as
Identifiers
What OpenQuestion holds
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.