Evidence map›Paper›PMID 27023466›Full record

Trial reportEuropean journal of clinical pharmacology2016

No major effects of vitamin D3 (1,25 dihydroxyvitamin D3) on absorption and pharmacokinetics of folic acid and fexofenadine in healthy volunteers.

Gerd A Kullak-Ublick, Christoph Gubler, Katharina Spanaus, Manfred G Ismair, Tatiana Claro da Silva, Alexander Jetter

Open access · hybridAbstract readClinical Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in European journal of clinical pharmacology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
3.3field-weighted citation impact, top 8% 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

6 citing papers in PubMed, 15 citations in OpenAlex.

  1. Trial
  2. Review
  3. Article
  4. Review
  5. Article
  6. 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

6 authors at 2 institutions in 1 country.

Gerd A Kullak-UblickDepartment of Clinical Pharmacology and Toxicology, University Hospital Zurich, University of Zurich, Rämistrasse 100, CH-8091, Zürich, Switzerland.
Christoph GublerDepartment of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, Zürich, Switzerland.
Katharina SpanausDepartment of Clinical Chemistry, University Hospital Zurich, University of Zurich, Zürich, Switzerland.
Manfred G IsmairXenoGesis Ltd, Nottingham, UK.
Tatiana Claro da SilvaDepartment of Clinical Pharmacology and Toxicology, University Hospital Zurich, University of Zurich, Rämistrasse 100, CH-8091, Zürich, Switzerland.
Alexander JetterDepartment of Clinical Pharmacology and Toxicology, University Hospital Zurich, University of Zurich, Rämistrasse 100, CH-8091, Zürich, Switzerland. alexander.jetter@usz.ch.
University Hospital of Zurich · CHUniversity of Zurich · CH

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

purposeIn Caco-2 cells, folate uptake via the proton-coupled folate transporter (PCFT) increases significantly by a 3-day treatment with 1,25-dihydroxyvitamin D3 (1,25(OH)2D3). Additionally, mRNA content and protein expression of the transporter OATP1A2 were increased up to ninefold with 1,25(OH)2D3. We investigated whether these in vitro findings can be confirmed in humans in vivo.

methodsTen healthy volunteers (six women) received 5 mg folic acid orally once before and once together with the last intake of a 10-day course of 0.5 μg 1,25(OH)2D3 orally. One hundred twenty milligrams fexofenadine, an OATP1A2 substrate, was taken in 1 day before the first folic acid intake, and again on the ninth day of 1,25(OH)2D3 intake. Duodenal biopsies were taken for transporter mRNA assessments once before and once on the ninth or tenth day of the vitamin D3 course. Serum folic acid and fexofenadine concentrations were quantified with a chemiluminescence immunoassay and LC-MS/MS, respectively. Pharmacokinetics were compared between periods with standard bioequivalence approaches.

resultsWhile geometric mean folic acid AUC0-2h, which mainly reflects absorption, was 0.403 and 0.414 mg/L·h before and after the vitamin D3 course (geometric mean ratio (GMR), 1.027; 90 % confidence interval (90 % CI), 0.788-1.340), the geometric mean fexofenadine AUC0-2h was 1.932 and 2.761 mg/L·h, respectively (GMR, 1.429; 90 % CI, 0.890-2.294). PCFT- and OATP1A2-mRNA expressions in duodenal biopsies were essentially unchanged.

conclusionsNo significant changes in folic acid and fexofenadine absorption were observed after a 10-day course of 1,25(OH)2D3 in humans in vivo. This study underlines the importance of confirming in vitro findings in vivo in humans.

Indexed as

Administration, OralAdultATP-Binding Cassette, Sub-Family C ProteinsATP Binding Cassette Transporter, Subfamily B, Member 1DuodenumFemaleFolic AcidHealthy VolunteersHumansIntestinal AbsorptionMaleOrganic Anion TransportersProton-Coupled Folate TransporterRNA, MessengerTerfenadineVitamin DATP-Binding Cassette, Sub-Family C ProteinsATP Binding Cassette Transporter, Subfamily B, Member 1dihydroxy-vitamin D3fexofenadineFolic Acidmultidrug resistance-associated protein 3Organic Anion TransportersProton-Coupled Folate TransporterRNA, MessengerSLC46A1 protein, humanSLCO1A2 protein, humanSLCO2B1 protein, humanTerfenadineVitamin D1,25-dihydroxyvitamin D3AbsorptionFexofenadineFolic acidOATP1A2PCFT

Identifiers

PMID27023466
PMCPMC4909797
OpenAlexW2328185806

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Registered trials

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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.