Evidence mapPaperPMID 33825113Full record

ArticlePharmaceutical research2021

Chiral Transplacental Pharmacokinetics of Fexofenadine: Impact of P-Glycoprotein Inhibitor Fluoxetine Using the Human Placental Perfusion Model.

Leonardo Pinto, Priya Bapat, Fernanda de Lima Moreira, Angelika Lubetsky, Ricardo de Carvalho Cavalli, Howard Berger, Vera Lucia Lanchote, Gideon Koren

Abstract read
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In one paragraph

Article in Pharmaceutical research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
0.4field-weighted citation impact, top 36% of its field
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

5 citing papers in PubMed, 6 citations in OpenAlex.

  1. Review
  2. A Mechanistic Physiologically Based Pharmacokinetic (PBPK) modeling approach for fexofenadine: predictive pharmacokinetic insights in humans.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2025
    Article
  3. Review
  4. Article
  5. Overview of Drug Transporters in Human Placenta.International journal of molecular sciences · 2021
    Review
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

8 authors at 6 institutions in 3 countries.

Leonardo PintoDepartment of Clinical Analysis, Food Science and Toxicology School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil. leonardopinto84@gmail.com.ORCID https://orcid.org/0000-0002-3578-4525
Priya BapatDivision of Clinical Pharmacology and Toxicology, The Hospital for Sick Children, Toronto, Ontario, Canada.
Fernanda de Lima MoreiraDepartment of Clinical Analysis, Food Science and Toxicology School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil.ORCID https://orcid.org/0000-0001-7699-2665
Angelika LubetskyDivision of Clinical Pharmacology and Toxicology, The Hospital for Sick Children, Toronto, Ontario, Canada.
Ricardo de Carvalho CavalliDepartment of Obstetrics and Gynecology School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil.
Howard BergerDepartment of Obstetrics and Gynecology, St. Michael's Hospital, Toronto, Ontario, Canada.
Vera Lucia LanchoteDepartment of Clinical Analysis, Food Science and Toxicology School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil.ORCID https://orcid.org/0000-0002-0074-4953
Gideon KorenAdelson Faculty of Medicine, Ariel University, Ariel, Israel.
Universidade de São Paulo · BRAriel University · ILHospital for Sick Children · CASt. Michael's Hospital · CAUniversidade de Ribeirão Preto · BRUniversity of Toronto · CA

Funding

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior BEX6119/13-1
6 · The paper itself

Abstract

purposeFexofenadine is a well-identified in vivo probe substrate of P-glycoprotein (P-gp) and/or organic anion transporting polypeptide (OATP). This work aimed to investigate the transplacental pharmacokinetics of fexofenadine enantiomers with and without the selective P-gp inhibitor fluoxetine.

methodsThe chiral transplacental pharmacokinetics of fexofenadine-fluoxetine interaction was determined using the ex vivo human placenta perfusion model (n = 4). In the Control period, racemic fexofenadine (75 ng of each enantiomer/ml) was added in the maternal circuit. In the Interaction period, racemic fluoxetine (50 ng of each enantiomer/mL) and racemic fexofenadine (75 ng of each enantiomer/mL) were added to the maternal circulation. In both periods, maternal and fetal perfusate samples were taken over 90 min.

resultsThe (S)-(-)- and (R)-(+)-fexofenadine fetal-to-maternal ratio values in Control and Interaction periods were similar (~0.18). The placental transfer rates were similar between (S)-(-)- and (R)-(+)-fexofenadine in both Control (0.0024 vs 0.0019 min

conclusionsOur study showed a low extent, slow rate of non-enantioselective placental transfer of fexofenadine enantiomers, indicating a limited fetal fexofenadine exposure mediated by placental P-gp and/or OATP2B1. The fluoxetine interaction did not affect the non-enantioselective transplacental transfer of fexofenadine. The ex vivo placental perfusion model accurately predicts in vivo placental transfer of fexofenadine enantiomers with remarkably similar values (~0.17), and thus estimates the limited fetal exposure.

Indexed as

Area Under CurveATP Binding Cassette Transporter, Subfamily BDrug InteractionsFemaleFluoxetineHistamine H1 Antagonists, Non-SedatingHumansMaternal-Fetal ExchangePerfusionPlacentaPregnancyPregnancy ComplicationsStereoisomerismTerfenadineABCB1 protein, humanATP Binding Cassette Transporter, Subfamily BfexofenadineFluoxetineHistamine H1 Antagonists, Non-SedatingTerfenadinedrug transportersfexofenadinefluoxetineplacentapregnancy

Identifiers

PMID33825113
OpenAlexW3152045758

What Socratic holds

Textmetadata
Read underepoch 390

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.