Trial reportBritish journal of clinical pharmacology2006
Different effects of fluvoxamine on rabeprazole pharmacokinetics in relation to CYP2C19 genotype status.
Trial report in British journal of clinical pharmacology, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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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.
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.
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Who cites it
15 citing papers in PubMed, 34 citations in OpenAlex.
- Effects of diltiazem on pharmacokinetics of tacrolimus in relation to CYP3A5 genotype status in renal recipients: from retrospective to prospective.The pharmacogenomics journal · 2011Trial
- Effect of CYP2C19 genotypes on the pharmacokinetic/pharmacodynamic relationship of rabeprazole after a single oral dose in healthy Chinese volunteers.European journal of clinical pharmacology · 2010Trial
- Differential genotype dependent inhibition of CYP2C9 in humans.Drug metabolism and disposition: the biological fate of chemicals · 2008Trial
- Identification of the time-point which gives a plasma rabeprazole concentration that adequately reflects the area under the concentration-time curve.European journal of clinical pharmacology · 2006Trial
- Effects of clarithromycin and verapamil on rabeprazole pharmacokinetics between CYP2C19 genotypes.European journal of clinical pharmacology · 2006Trial
- Insight into Risk Factors, Pharmacogenetics/Genomics, and Management of Adverse Drug Reactions in Elderly: A Narrative Review.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Rates of Divergent Pharmacogenes in a Psychiatric Cohort of Inpatients with Depression-Arguments for Preemptive Testing.Journal of xenobiotics · 2022Article
- Optimising Seniors' Metabolism of Medications and Avoiding Adverse Drug Events Using Data on How Metabolism by Their P450 Enzymes Varies with Ancestry and Drug-Drug and Drug-Drug-Gene Interactions.Journal of personalized medicine · 2020Article
- Drug-drug-gene interactions and adverse drug reactions.The pharmacogenomics journal · 2020Review
- Review
- Inhibition of baicalin on metabolism of phenacetin, a probe of CYP1A2, in human liver microsomes and in rats.PloS one · 2014Article
- Impact of genetic polymorphism on drug-drug interactions mediated by cytochromes: a general approach.The AAPS journal · 2013Article
- In vivo quantitative prediction of the effect of gene polymorphisms and drug interactions on drug exposure for CYP2C19 substrates.The AAPS journal · 2013Article
- Drug-drug interaction profiles of proton pump inhibitors.Clinical pharmacokinetics · 2010Review
- Proton pump inhibitors: an update of their clinical use and pharmacokinetics.European journal of clinical pharmacology · 2008Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsRabeprazole is known to be a substrate of CYP2C19. Our objective was to evaluate the possible effect of an inhibitor of CYP2C19, fluvoxamine, and compare the inhibitory effect of fluvoxamine on the metabolism of rabeprazole between CYP2C19 genotypes.
methodsA two-way randomized double-blind, placebo-controlled crossover study was performed. Twenty-one volunteers, of whom seven were homozygous extensive metabolizers (EMs), eight were heterozygous EMs and six were poor metabolizers (PMs) for CYP2C19, received two 6-day courses of either fluvoxamine 50 mg or placebo daily in a randomized fashion with a single oral dose of rabeprazole 20 mg on day 6 in all cases. Plasma concentrations of rabeprazole and its metabolite rabeprazole thioether were monitored up to 24 h after dosing.
resultsDuring placebo administration, the mean AUCs(0,infinity) of rabeprazole in homozygous EMs, heterozygous EMs and PMs were 882 (95% CI, 602, 1162) ng ml-1h , 1214 (975, 1453) ng ml-1 h and 2762 (2482, 3042) ng ml-1 h (P<0.001), respectively. Fluvoxamine treatment increased AUC(0,infinity) of rabeprazole and rabeprazole thioether by 2.8-fold (P<0.001) and 5.1-fold (P<0.01) in homozygous EMs, and by 1.7-fold (P<0.01) and 2.6-fold (P<0.01) in heterozygous EMs, and significantly prolonged the elimination half-life of rabeprazole and rabeprazole thioether in homozygous EMs and in heterozygous EMs, whereas no difference in any pharmacokinetic parameters was found in PMs. There was a significant difference in fluvoxamine-mediated percentage increase in AUC(0,infinity) of rabeprazole and rabeprazole thioether between CYP2C19 genotypes.
conclusionsThe present study indicates that there are significant drug interactions between rabeprazole and fluvoxamine in EMs of CYP2C19. It is predominantly involved in rabeprazole and rabeprazole thioether metabolism in EMs. Therefore, CYP2C19 is the key determinant of rabeprazole disposition in EMs.
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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.