Evidence map›Paper›PMID 28929443›Full record

Trial reportEuropean journal of drug metabolism and pharmacokinetics2018

Short-Term Fasting Alters Pharmacokinetics of Cytochrome P450 Probe Drugs: Does Protein Binding Play a Role?

Laureen A Lammers, Roos Achterbergh, Johannes A Romijn, Ron A A Mathôt

Abstract readRandomized Controlled Trial
In one paragraph

Trial report in European journal of drug metabolism and pharmacokinetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed, 1 pooled it
–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

4 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Article
  3. Review
  4. 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

4 authors.

Laureen A LammersDepartment of Hospital Pharmacy, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands. l.a.tenberg-lammers@amc.uva.nl.
Roos AchterberghDepartment of Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Johannes A RomijnDepartment of Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Ron A A MathôtDepartment of Hospital Pharmacy, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

BACKGROUND AND

objectivesShort-term fasting differentially alters cytochrome P450 (CYP) mediated drug metabolism. This has been established by using CYP-enzyme selective probe drugs. However, the observed effects of fasting on the pharmacokinetics of these probe drugs may also include the effects of altered plasma protein binding of these drugs. Therefore, we studied the effect of short-term fasting on protein binding of five commonly used probe drugs [caffeine (CYP1A2), metoprolol (CYP2D6), midazolam (CYP3A4), omeprazole (CYP2C19) and S-warfarin (CYP2C9)].

methodsThe free and total plasma concentrations of the five probe drugs were analyzed by LC-MS/MS in samples retrieved in a cross-over study in which nine healthy subjects received an intravenous administration of the cocktail after an overnight fast (control) and after 36 h of fasting.

resultsShort-term fasting increased plasma free fatty acid concentrations from 0.48 mmol/L (control) to 1.29 mmol/L (36 h fasting) (p = 0.012). Short-term fasting did not alter the free fractions of caffeine, metoprolol and omeprazole compared to the control intervention (p > 0.05). Power to detect a difference for midazolam and S-warfarin was low since the majority of free concentrations were below the limit of quantification.

conclusionsThis study demonstrates that short-term fasting does not alter protein binding of the probe drugs caffeine, metoprolol and omeprazole.

Indexed as

Administration, IntravenousCaffeineCross-Over StudiesCytochrome P-450 Enzyme SystemFastingHumansMaleMetoprololMidazolamOmeprazolePharmaceutical PreparationsProtein BindingWarfarinCaffeineCytochrome P-450 Enzyme SystemMetoprololMidazolamOmeprazolePharmaceutical PreparationsWarfarin

Identifiers

PMID28929443
PMCPMC5854751

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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.