Evidence map›Paper›PMID 36271205›Full record

Trial reportPharmaceutical research2022

Microdialysis of Voriconazole and its N-Oxide Metabolite: Amalgamating Knowledge of Distribution and Metabolism Processes in Humans.

Josefine Schulz, Robin Michelet, Markus Zeitlinger, Gerd Mikus, Charlotte Kloft

Open access · hybridAbstract readClinical Trial
In one paragraph

Trial report in Pharmaceutical research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.3field-weighted citation impact, top 43% 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

3 citing papers in PubMed, 3 citations in OpenAlex.

  1. Review
  2. Article
  3. 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

5 authors at 3 institutions in 2 countries.

Josefine SchulzDepartment of Clinical Pharmacy & Biochemistry, Institute of Pharmacy, Freie Universitaet Berlin, Kelchstraße 31, 12169, Berlin, Germany.
Robin MicheletDepartment of Clinical Pharmacy & Biochemistry, Institute of Pharmacy, Freie Universitaet Berlin, Kelchstraße 31, 12169, Berlin, Germany.
Markus ZeitlingerDepartment of Clinical Pharmacology, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.
Gerd MikusDepartment of Clinical Pharmacy & Biochemistry, Institute of Pharmacy, Freie Universitaet Berlin, Kelchstraße 31, 12169, Berlin, Germany.
Charlotte KloftDepartment of Clinical Pharmacy & Biochemistry, Institute of Pharmacy, Freie Universitaet Berlin, Kelchstraße 31, 12169, Berlin, Germany. charlotte.kloft@fu-berlin.de.
Freie Universität Berlin · DEHeidelberg University · DEMedical University of Vienna · AT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

purposeVoriconazole is an essential antifungal drug whose complex pharmacokinetics with high interindividual variability impedes effective and safe therapy. By application of the minimally-invasive sampling technique microdialysis, interstitial space fluid (ISF) concentrations of VRC and its potentially toxic N-oxide metabolite (NO) were assessed to evaluate target-site exposure for further elucidating VRC pharmacokinetics.

methodsPlasma and ISF samples of a clinical trial with an approved VRC dosing regimen were analyzed for VRC and NO concentrations. Concentration-time profiles, exposure assessed as area-under-the-curve (AUC) and metabolic ratios of four healthy adults in plasma and ISF were evaluated regarding the impact of multiple dosing and CYP2C19 genotype.

resultsVRC and NO revealed distribution into ISF with AUC values being ≤2.82- and 17.7-fold lower compared to plasma, respectively. Intraindividual variability of metabolic ratios was largest after the first VRC dose administration while interindividual variability increased with multiple dosing. The CYP2C19 genotype influenced interindividual differences with a maximum 6- and 24-fold larger AUC

conclusionThe feasibility of the simultaneous microdialysis of VRC and NO in vivo was demonstrated and provided new quantitative insights by leveraging distribution and metabolism processes of VRC in humans. The exploratory analysis suggested substantial dissimilarities of VRC and NO pharmacokinetics in plasma and ISF. Ultimately, a thorough understanding of target-site pharmacokinetics might contribute to the optimization of personalized VRC dosing regimens.

Indexed as

Antifungal AgentsPlasmaAdultCytochrome P-450 CYP2C19HumansMicrodialysisVoriconazoleAntifungal AgentsCytochrome P-450 CYP2C19Voriconazoledrug metabolismmicrodialysispharmacogeneticspharmacokineticsvoriconazole

Identifiers

PMID36271205
PMCPMC9780129
OpenAlexW4307026372

What Socratic holds

Textmetadata
LicenceCC BY
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.