Evidence mapPaperPMID 41289433Full record

ArticleCPT: pharmacometrics & systems pharmacology2026

Comparison of Metformin PBPK Models Incorporating Placental Transfer to Predict Fetal and Maternal Exposure.

Jacqueline B Tiley, Mattie E Hartauer, Tajhia L Whigham, Maïlys De Sousa Mendes, Kim L R Brouwer, Mary F Hebert

Abstract readComparative Study
In one paragraph

Article in CPT: pharmacometrics & systems pharmacology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
field-weighted citation impact
1 · What the graph read from 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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors.

Jacqueline B TileyDivision of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.ORCID https://orcid.org/0000-0002-9977-1184
Mattie E HartauerDivision of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.ORCID https://orcid.org/0000-0002-5082-0168
Tajhia L WhighamDivision of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.ORCID https://orcid.org/0000-0003-0622-1034
Maïlys De Sousa MendesSimcyp Division, Certara UK Limited, Sheffield, UK.ORCID https://orcid.org/0000-0001-5460-4350
Kim L R BrouwerDivision of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.ORCID https://orcid.org/0000-0003-1945-4929
Mary F HebertDepartment of Pharmacy, University of Washington, Seattle, Washington, USA.ORCID https://orcid.org/0000-0002-2530-8189

Funding

UW Obstetric-Fetal Pharmacology Research UnitU10HD047892 · UNIVERSITY OF WASHINGTON · 2004 to 2005
$1.7M
Integrated Transporter Elucidation CenterUC2HD113039 · RUTGERS BIOMEDICAL AND HEALTH SCIENCES · 2025 to 2025
$1.2M
PBPK Modeling & Simulation to Predict Transporter-Mediated Drug Secretion into Human Breast MilkR01HD112282 · UNIVERSITY OF WASHINGTON · 2025 to 2025
$828k
Mechanisms of Altered Hepatic Transport: Impact on Drug TherapyR35GM122576 · UNIV OF NORTH CAROLINA CHAPEL HILL · 2025 to 2025
$607k
NICHD NIH HHS R01 HD112282NICHD NIH HHS U10 HD047892NICHD NIH HHS UC2 HD113039NIGMS NIH HHS R35 GM122576
6 · The paper itself

Abstract

Physiologically based pharmacokinetic (PBPK) modeling of placental drug transfer is an evolving tool for predicting fetal drug exposure. In this study, a pregnancy-specific metformin PBPK model was developed, and the following four approaches were evaluated to predict metformin placental transfer: (1) perfusion-limited model, and permeability-limited models using (2) ex vivo cotyledon open system apparent clearance, (3) ex vivo cotyledon closed system data fit to a three-compartment model to estimate clearance, and (4) active transport kinetics and passive clearance. Simulated metformin maternal plasma concentrations (MPCs) and umbilical cord venous plasma concentrations (UCCs) were compared to observed in vivo data from subjects with gestational diabetes mellitus taking metformin 500 mg twice daily. Model selection criteria were determined by the percentage of observed clinical data falling within the 5th to 95th percentiles of the simulated population. Among the approaches, the model that included passive permeability and in vitro intrinsic transporter clearances (Approach 4) best described placental metformin transfer, with 92% of UCCs falling within the 5th to 95th percentiles of the simulated population. Furthermore, maternal uptake transport had the largest influence on predicted UCCs. A two-fold increase in maternal uptake transport increased the predicted population mean UCC C

Indexed as

Hypoglycemic AgentsMaternal-Fetal ExchangeMetforminModels, BiologicalPlacentaAdultBiological TransportDiabetes, GestationalFemaleFetal BloodFetusHumansMaternal ExposurePregnancyHypoglycemic AgentsMetformindrug transportfetusmathematical modelingmetforminpregnancy

Identifiers

PMID41289433
PMCPMC12823317

What Socratic holds

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LicenceCC BY-NC
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Registered trials

None linked

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 Socratic graph.