Evidence map›Paper›PMID 18294333›Full record

Trial reportBritish journal of clinical pharmacology2008

Increased omeprazole metabolism in carriers of the CYP2C19*17 allele; a pharmacokinetic study in healthy volunteers.

R Michael Baldwin, Staffan Ohlsson, Rasmus Steen Pedersen, Jessica Mwinyi, Magnus Ingelman-Sundberg, Erik Eliasson, Leif Bertilsson

Registry-linked trialOpen access · bronzeAbstract readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in British journal of clinical pharmacology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03650543 (Effect of the CYP2C19 Polymorphism in Helicobacter Pylori Eradication), which is not on this map. Cited by 76 papers.

0numbers the graph read from it
0cells of the map it votes in
76citing papers in PubMed
16.7field-weighted citation impact, top 1% 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.

NCT03650543 phase4completednot on this mapstarted 2012, after this paper: background citation

Effect of the CYP2C19 Polymorphism in Helicobacter Pylori Eradication

TypeinterventionalSponsorJaveriana UniversityRan2012 to 2015Enrolled133ConditionsCYP2C19 Polymorphism, H.Pylori Infection, TherapyArmsamoxicillin clarithromycin omeprazole 1, amoxicillin clarithromycin omeprazole 2
3 · Its place in the literature

Who cites it

76 citing papers in PubMed, 143 citations in OpenAlex.

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  18. Impact of Pharmacogenomics in Clinical Practice.Pharmaceuticals (Basel, Switzerland) · 2023
    Review
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16 more citing papers are in PubMed but not listed here.

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

7 authors at 2 institutions in 1 country.

R Michael BaldwinSection of Pharmacogenetics, Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden. mike.baldwin@ki.se
Staffan Ohlsson
Rasmus Steen Pedersen
Jessica Mwinyi
Magnus Ingelman-Sundberg
Erik Eliasson
Leif Bertilsson
Karolinska Institutet · SEKarolinska University Hospital · SE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

what is already known about this subjectThe only existing study of CYP2C19*17-associated alterations in drug pharmacokinetics was retrospective and compared probe drug metabolic ratios. The CYP2C19*17 allele had been associated with a two- and fourfold decrease in omeprazole and S/R-mephenytoin metabolic ratios. WHAT THIS STUDY ADDS: This study characterized the single-dose pharmacokinetics of omeprazole, along with the 5-hydroxy and sulphone metabolites, in CYP2C19*17/*17 and CYP2C19*1/*1 subjects. The observed differences in omeprazole AUC(infinity) suggest that the CYP2C19*17 allele is an important explanatory factor behind individual cases of therapeutic failure. AIMS To investigate the influence of the CYP2C19*17 allele on the pharmacokinetics of omeprazole, a commonly used CYP2C19 probe drug, in healthy volunteers.

methodsIn a single-dose pharmacokinetic study, 17 healthy White volunteers genotyped as either CYP2C19*17/*17 or CYP2C19*1/*1 received an oral dose of 40 mg of omeprazole. Plasma was sampled for up to 10 h postdose, followed by quantification of omeprazole, 5-hydroxy omeprazole and omeprazole sulphone by high-performance liquid chromatography.

resultsThe mean omeprazole AUC(infinity) of 1973 h nmol l(-1) in CYP2C19*17/*17 subjects was 2.1-fold lower [95% confidence interval (CI) 1.1, 3.3] than in CYP2C19*1/*1 subjects (4151 h nmol l(-1), P = 0.04). A similar trend was observed for the sulphone metabolite with the CYP2C19*17/*17 group having a mean AUC(infinity) of 1083 h nmol l(-1), 3.1-fold lower (95% CI 1.2, 5.5) than the CYP2C19*1/*1 group (3343 h nmol l(-1), P = 0.03). A pronounced correlation (r(2) = 0.95, P < 0.0001) was seen in the intraindividual omeprazole AUC(infinity) and omeprazole sulphone AUC(infinity) values.

conclusionsThe pharmacokinetics of omeprazole and omeprazole sulphone differ significantly between homozygous CYP2C19*17 and CYP2C19*1 subjects. For clinically important drugs that are metabolized predominantly by CYP2C19, the CYP2C19*17 allele might be associated with subtherapeutic drug exposure.

Indexed as

Polymorphism, GeneticAdultAllelesAnti-Ulcer AgentsArea Under CurveAryl Hydrocarbon HydroxylasesCytochrome P-450 CYP2C19FemaleGenotypeHumansMaleMiddle AgedMixed Function OxygenasesOmeprazoleAnti-Ulcer AgentsAryl Hydrocarbon HydroxylasesCYP2C19 protein, humanCytochrome P-450 CYP2C19Mixed Function OxygenasesOmeprazole

Identifiers

PMID18294333
PMCPMC2432489
OpenAlexW2121858592

What OpenQuestion holds

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Registered trials

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.