ArticleClinical pharmacokinetics2018
Prediction of Fetal Darunavir Exposure by Integrating Human Ex-Vivo Placental Transfer and Physiologically Based Pharmacokinetic Modeling.
Article in Clinical pharmacokinetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.
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
27 citing papers in PubMed, 1 synthesis or guideline pooled it, 50 citations in OpenAlex.
- Barriers and Facilitators for Bringing Model-Informed Precision Dosing to the Patient's Bedside: A Systematic Review.Clinical pharmacology and therapeutics · 2025Pooled it
- Advancing Pregnancy and Pediatric Science through the NIH Transporter Elucidation Network.Clinical pharmacology and therapeutics · 2026Review
- PBPK Models for Fetal Drug Exposure: A Critical Assessment of Current Approaches and Regulatory Readiness.Journal of clinical pharmacology · 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
- Evaluation of Various Approaches to Estimate Transplacental Clearance of Vancomycin for Predicting Fetal Concentrations using a Maternal-Fetal Physiologically Based Pharmacokinetic Model.Pharmaceutical research · 2024Article
- Predicting Human Fetal Drug Exposure Through Maternal-Fetal PBPK Modeling and In Vitro or Ex Vivo Studies.Journal of clinical pharmacology · 2022Review
- Applications, Challenges, and Outlook for PBPK Modeling and Simulation: A Regulatory, Industrial and Academic Perspective.Pharmaceutical research · 2022Review
- 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
- The Role of the 3Rs for Understanding and Modeling the Human Placenta.Journal of clinical medicine · 2021Review
- 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
- Prediction of Maternal and Fetal Pharmacokinetics of Dolutegravir and Raltegravir Using Physiologically Based Pharmacokinetic Modeling.Clinical pharmacokinetics · 2020Article
- Innovative Approaches for Pharmacology Studies in Pregnant and Lactating Women: A Viewpoint and Lessons from HIV.Clinical pharmacokinetics · 2020Article
- Anatomical and physiological alterations of pregnancy.Journal of pharmacokinetics and pharmacodynamics · 2020Review
- Drug dosing during pregnancy-opportunities for physiologically based pharmacokinetic models.Journal of pharmacokinetics and pharmacodynamics · 2020Review
- Integration of Placental Transfer in a Fetal-Maternal Physiologically Based Pharmacokinetic Model to Characterize Acetaminophen Exposure and Metabolic Clearance in the Fetus.Clinical pharmacokinetics · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundFetal antiretroviral exposure is usually derived from the cord-to-maternal concentration ratio. This static parameter does not provide information on the pharmacokinetics in utero, limiting the assessment of a fetal exposure-effect relationship.
objectiveThe aim of this study was to incorporate placental transfer into a pregnancy physiologically based pharmacokinetic model to simulate and evaluate fetal darunavir exposure at term.
methodsAn existing and validated pregnancy physiologically based pharmacokinetic model of maternal darunavir/ritonavir exposure was extended with a feto-placental unit. To parameterize the model, we determined maternal-to-fetal and fetal-to-maternal darunavir/ritonavir placental clearance with an ex-vivo human cotyledon perfusion model. Simulated maternal and fetal pharmacokinetic profiles were compared with observed clinical data to qualify the model for simulation. Next, population fetal pharmacokinetic profiles were simulated for different maternal darunavir/ritonavir dosing regimens.
resultsAn average (±standard deviation) maternal-to-fetal cotyledon clearance of 0.91 ± 0.11 mL/min and fetal-to-maternal clearance of 1.6 ± 0.3 mL/min was determined (n = 6 perfusions). Scaled placental transfer was integrated into the pregnancy physiologically based pharmacokinetic model. For darunavir 600/100 mg twice a day, the predicted fetal maximum plasma concentration, trough concentration, time to maximum plasma concentration, and half-life were 1.1, 0.57 mg/L, 3, and 21 h, respectively. This indicates that the fetal population trough concentration is higher or around the half-maximal effective darunavir concentration for a resistant virus (0.55 mg/L).
conclusionsThe results indicate that the population fetal exposure after oral maternal darunavir dosing is therapeutic and this may provide benefits to the prevention of mother-to-child transmission of human immunodeficiency virus. Moreover, this integrated approach provides a tool to prevent fetal toxicity or enhance the development of more selectively targeted fetal drug treatments.
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.