Evidence map›Paper›PMID 30167757›Full record

Trial reportEuropean journal of clinical pharmacology2018

Voriconazole greatly increases the exposure to oral buprenorphine.

Mari Fihlman, Tuija Hemmilä, Nora M Hagelberg, Janne T Backman, Jouko Laitila, Kari Laine, Pertti J Neuvonen, Klaus T Olkkola, Teijo I Saari

Open access · greenAbstract readRandomized Controlled Trial
PubMed Publisher
In one paragraph

Trial report in European journal of clinical pharmacology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed, 1 pooled it
1.6field-weighted citation impact, top 16% 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

8 citing papers in PubMed, 1 synthesis or guideline pooled it, 14 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Article
  4. Article
  5. Article
  6. Review
  7. Article
  8. 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

9 authors at 3 institutions in 1 country.

Mari FihlmanDepartment of Anaesthesiology and Intensive Care, University of Turku, P.O. Box 52, Kiinamyllynkatu 4-8, FI-20520, Turku, Finland.
Tuija HemmiläDivision of Perioperative Services, Intensive Care and Pain Medicine, Turku University Hospital, Turku, Finland.
Nora M HagelbergDepartment of Anaesthesiology and Intensive Care, University of Turku, P.O. Box 52, Kiinamyllynkatu 4-8, FI-20520, Turku, Finland.
Janne T BackmanDepartment of Clinical Pharmacology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
Jouko LaitilaDepartment of Clinical Pharmacology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
Kari LaineDepartment of Pharmacology, Drug Development and Therapeutics, University of Turku, Turku, Finland.
Pertti J NeuvonenDepartment of Clinical Pharmacology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
Klaus T OlkkolaDepartment of Anaesthesiology, Intensive Care and Pain Medicine, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
Teijo I SaariDepartment of Anaesthesiology and Intensive Care, University of Turku, P.O. Box 52, Kiinamyllynkatu 4-8, FI-20520, Turku, Finland. teisaa@utu.fi.ORCID http://orcid.org/0000-0003-1225-4561
University of Helsinki · FIUniversity of Turku · FITurku University Hospital · FI

Funding

Governmental research grant 13821
6 · The paper itself

Abstract

purposeBuprenorphine has low oral bioavailability. Regardless of sublingual administration, a notable part of buprenorphine is exposed to extensive first-pass metabolism by the cytochrome P450 (CYP) 3A4. As drug interaction studies with buprenorphine are limited, we wanted to investigate the effect of voriconazole, a strong CYP3A4 inhibitor, on the pharmacokinetics and pharmacodynamics of oral buprenorphine.

methodsTwelve healthy volunteers were given either placebo or voriconazole (orally, 400 mg twice on day 1 and 200 mg twice on days 2-5) for 5 days in a randomized, cross-over study. On day 5, they ingested 0.2 mg (3.6 mg during placebo phase) oral buprenorphine. We measured plasma and urine concentrations of buprenorphine and norbuprenorphine and monitored their pharmacological effects. Pharmacokinetic parameters were normalized for a buprenorphine dose of 1.0 mg.

resultsVoriconazole greatly increased the mean area under the plasma concentration-time curve (AUC

conclusionsVoriconazole greatly increases exposure to oral buprenorphine, mainly by inhibiting intestinal and liver CYP3A4. Effect on some transporters may explain elevated norbuprenorphine concentrations. Although oral buprenorphine is not commonly used, this interaction may become relevant in patients receiving sublingual buprenorphine together with voriconazole or other CYP3A4 or transporter inhibitors.

Indexed as

AdolescentAdultAnalgesics, OpioidAntifungal AgentsArea Under CurveBiotransformationBuprenorphineCross-Over StudiesCytochrome P-450 CYP3ADizzinessDrug InteractionsFemaleHalf-LifeHealthy VolunteersHumansMaleAnalgesics, OpioidAntifungal AgentsBuprenorphineCYP3A4 protein, humanCytochrome P-450 CYP3AnorbuprenorphineVoriconazoleBuprenorphineCYP3A4Drug-drug interactionNorbuprenorphinePharmacokineticsTransportersVoriconazole

Identifiers

PMID30167757
OpenAlexW2889424942

What OpenQuestion 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 OpenQuestion graph.