ArticleEuropean journal of clinical pharmacology2015
Lower CYP2C9 activity in Turkish patients with Behçet's disease compared to healthy subjects: a down-regulation due to inflammation?
Article in European journal of clinical pharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers, 2 of them syntheses that pooled it.
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Who cites it
8 citing papers in PubMed, 2 syntheses or guidelines pooled it, 16 citations in OpenAlex.
- Clinically important alterations in pharmacogene expression in histologically severe nonalcoholic fatty liver disease.Nature communications · 2023Pooled it
- Impact of Inflammation on Cytochromes P450 Activity in Pediatrics: A Systematic Review.Clinical pharmacokinetics · 2021Pooled it
- Drug-disease interaction: Clinical consequences of inflammation on drugs action and disposition.Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques · 2023Review
- Impact of Acute Inflammation on Cytochromes P450 Activity Assessed by the Geneva Cocktail.Clinical pharmacology and therapeutics · 2021Observational
- Influence of Inflammation on Cytochromes P450 Activity in Adults: A Systematic Review of the Literature.Frontiers in pharmacology · 2021Review
- Phenoconversion of Cytochrome P450 Metabolism: A Systematic Review.Journal of clinical medicine · 2020Review
- Increased risk for cerebral ischemic stroke in diabetes: genetically polymorphic CYP mediated production of neuroprotective EETs and sulfonylurea metabolism in relation with KActa pharmacologica Sinica · 2019Article
- Pharmacogenetics and precision medicine: Is inflammation a covert threat to effective genotype-based therapy?Therapeutic advances in drug safety · 2017Article
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Authors and funding
11 authors at 4 institutions in 3 countries.
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No grant is acknowledged in the PubMed record.
Abstract
backgroundWe previously reported on a Swedish patient with Behçet's disease (BD) who was an ultra-rapid metaboliser of drugs catalysed by CYP2C9. Was this extreme metabolism caused by the disease?
aimThis study aims to compare the genotype/phenotype of CYP2C9 in patients with BD and healthy subjects. As the occurrence of BD is high in Turkey, all subjects were recruited from this country.
methodsGenotyping of CYP2C9 was performed using standard PCR-RFLP and allele-specific PCR methods. Phenotyping of CYP2C9 was performed by administration of a 50-mg single oral dose of losartan and by calculating the urinary metabolic ratio (MR) of probe drug to its metabolite E-3174. Quantitation was performed by HPLC.
resultsThe frequency of CYP2C9*2 and *3 was not significantly different between the Behçet's disease patients (12.5 and 8.7%) and the healthy subjects (8.9 and 8.2%). The geometric mean losartan MR was higher in the 52 patients (1.75) than in the 96 healthy subjects (1.02) (p = 0.002; t-test). Within the genotypes *1/*1, there was a significant difference of MR between patients and healthy subjects (P = 0.006). All but three of the Behçet's disease patients were treated with colchicine. In nine subsequent patients, we found no significant effect of 2 weeks of treatment with colchicine on the CYP2C9 MR.
conclusionContrary to expectation, the CYP2C9 activity was lower in Turkish BD patients compared to healthy subjects. As this seems not to be due to colchicine treatment, our hypothesis is that inflammation related to BD might have caused the down-regulation of the CYP2C9 activity due to immune cytokine reactions. The ultra-rapid metabolism of CYP2C9 substrate drugs in the Swedish patient was not due to her BD.
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