First-line eradication for<i>Helicobacter pylori</i>-positive gastritis by esomeprazole-based triple therapy is influenced by<i>CYP2C19</i>genotype

Saito, Yoshimasa

doi:10.3748/wjg.v21.i48.13548

Cited by 27 publications

(23 citation statements)

References 19 publications

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“…When these patients had their doses escalated, H. pylori eradication rate increased to about 80% [70], supporting the need for escalated doses in CYP2C19 NM phenotypes. Contrary to the results by Saito et al [62], that found significant effect of CYP2C19 genotype on H.pylori eradication in esomeprazole Schwab et al [71] did not document an effect for CYP2C19 genotype on GERD healing in a relatively large cohort of European patients (N = 205) who used esomeprazole. It is important to note that the study by Schwab et al was conducted before the discovery of *17 , and therefore *17 allele, which is present in 30% of patients with European ancestry was not assessed.…”

Section: Cyp2c19 and Ppi Pharmacogeneticscontrasting

confidence: 57%

“…Collectively, the data support better outcomes in management of GERD and higher success rate of H. pylori eradication in IM and PM phenotypes compared to NM, RM, and UM phenotypes (Table 4) [59,60,62–64], which is consistent with the higher intragastric pH achieved in patients with reduced CYP2C19 activity and higher PPI concentrations [77–79]. While many studies suggest this to be true regardless of the PPI used, some reports have suggested that the therapeutic outcomes are less influenced by genotype in PPIs with less dependence on CYP2C19 metabolism, namely rabeprazole and esomeprazole [71,73,80].…”

Section: Cyp2c19 and Ppi Pharmacogeneticsmentioning

confidence: 71%

“…That the genotype of CYP2C19 may affect the therapeutic outcomes of PPIs was demonstrated with a string of publications documenting lower intragastric pH 48,49,50 (Table 3) with diminished control of GERD symptoms 59,60,61, and lower eradication rates of H. pylori in patients with a NM phenotype status 62,63 (Table 4). As further evidence for the impact of genotype on therapeutic outcomes, Furuta et al 60.…”

Section: Cyp2c19 and Ppi Pharmacogeneticsmentioning

confidence: 99%

“…Specifically, CYP2C19 no function alleles were associated with higher eradication rates due to decreased clearance of PPIs and higher plasma levels. A recent study by Saito et al included 80 Japanese patients who were on esomeprazole-based H. pylori treatment at a daily dose of 40 mg (Table 4) [62]. The study found a statistically significant difference in eradication rates based on genotype.…”

Section: Cyp2c19 and Ppi Pharmacogeneticsmentioning

confidence: 99%

See 3 more Smart Citations

Proton pump inhibitors: from CYP2C19 pharmacogenetics to precision medicine

Rouby

Lima

Johnson

2018

Expert Opinion on Drug Metabolism & Toxicology

181

172

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Introduction: Proton Pump inhibitors (PPIs) are commonly used for a variety of acid related disorders. Despite the overall effectiveness and safety profile of PPIs, some patients do not respond adequately or develop treatment related adverse events. This variable response among patients is in part due to genotype variability of CYP2C19, the gene encoding the CYP450 (CYP2C19) isoenzyme responsible for PPIs metabolism.Areas covered: This article provides an overview of the pharmacokinetics and mechanism of action of the currently available PPIs, including the magnitude of CYPC19 contribution to their metabolism. Additionally, the role of CYP2C19 genetic variability in the therapeutic effectiveness or outcomes of PPI therapy is highlighted in details, to provide supporting evidence for the potential value of CYP2C19 genotype-guided approaches to PPI drug therapy.Expert opinion: There is a large body of evidence describing the impact of CYP2C19 variability on PPIs and its potential role in individualizing PPI therapy, yet, CYP2C19 pharmacogenetics has not been widely implemented into clinical practice. More data are needed but CYP2C19 genotype-guided dosing of PPIs is likely to become increasingly common and is expected to improve clinical outcomes, and minimize side effects related to PPIs.

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Section: Cyp2c19 and Ppi Pharmacogeneticscontrasting

confidence: 57%

Section: Cyp2c19 and Ppi Pharmacogeneticsmentioning

confidence: 71%

Section: Cyp2c19 and Ppi Pharmacogeneticsmentioning

confidence: 99%

Section: Cyp2c19 and Ppi Pharmacogeneticsmentioning

confidence: 99%

See 2 more Smart Citations

Proton pump inhibitors: from CYP2C19 pharmacogenetics to precision medicine

Rouby

Lima

Johnson

2018

Expert Opinion on Drug Metabolism & Toxicology

181

172

View full text Add to dashboard Cite

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“…The eradication rate using traditional first-line therapy is low (70%) due to the increase in CLR resistance 11,17,18. 14 The Japanese government insurance has allowed first-line (PPI-AMX-CLR) and second-line (PPI-AMX-MTZ) eradication therapy.…”

mentioning

confidence: 99%

Vonoprazan improves the efficacy of Helicobacter pylori eradication therapy with a regimen consisting of clarithromycin and metronidazole in patients allergic to penicillin

et al. 2017

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Association BetweenCYP2C19*17Alleles and pH Probe Testing Outcomes in Children With Symptomatic Gastroesophageal Reflux

Franciosi

Mougey

Williams

et al. 2017

The Journal of Clinical Pharma

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Esophageal pH monitoring remains a primary diagnostic tool for detecting gastroesophageal reflux disease (GERD). GERD that is refractory to proton pump inhibitor (PPI) medications may be related to CYP2C19 variants. Current PPI dosing practices in children do not take into account CYP2C19 allelic variants, which may lead to underdosing and subsequently to a misperception of PPI therapy failure. We hypothesized that pH probe acid exposure outcomes associate with CYP2C19*17 alleles among children with clinical concern for GERD. We identified a retrospective cohort of 74 children (age range 0.71-17.1 years, mean 8.5, SD 4.6) with stored endoscopic tissue samples and who had also undergone esophageal pH testing while on PPI therapy. These individuals were genotyped for common CYP2C19 alleles and were dichotomized to either CYP2C19*17 allelic carriers without corresponding loss of function alleles as cases vs controls. Associations between pH probe acid exposure outcomes and CYP2C19*17 alleles were investigated. Compared to controls, children who carry CYP2C19*17 alleles without corresponding loss-of-function alleles demonstrated statistically significant longer times with pH < 4 (76.46 vs 33.47 minutes, P = .03); and higher percent of time with pH < 4.0 (5.71 vs 2.67 minutes, P = .04). These findings remained statistically significant using multiple-regression modeling with test duration, PPI dose, and race as confounding variables. PPI therapy in children with *17 alleles may be better optimized with CYP2C19 genotype-guided dosing prior to pH probe testing. Keywords proton pump inhibitor, children, CYP2C19, GERDThe rate of gastroesophageal reflux disease (GERD) diagnoses in children has increased over the past decade with a concomitant rapid increase in the use of proton pump inhibitor (PPI) medications. 1 Esophageal pH monitoring remains the primary diagnostic tool for detecting refractory GERD (not responsive to PPI therapy). 2 When GERD that is refractory to PPI treatment in children is identified in clinical practice, genetic factors related to PPI metabolism are not generally thought to play a role. 3 The efficacy of PPIs to treat GERD and related conditions is closely linked to plasma concentrations. 4 All PPIs except rabeprazole undergo significant metabolism by CYP2C19, and genetic variation in CYP2C19 influences the pharmacokinetics of all PPIs. [5][6][7] The CYP2C19 gene is located on chromosome 10q24.1-q24.3, has 9 exons and is highly polymorphic. 8-10 Several loss-of-function (LOF) alleles (eg, CYP2C19*2 through *9) reduce drug clearance and significantly increase PPI plasma concentrations. Alleles carrying rs12248560 are termed *17, and individuals carrying 1 or 2 such alleles clear PPIs at a higher rate and have lower PPI plasma levels compared to carriers of LOF alleles. 3,[11][12][13] Studies have reported a variable range of 10% to 40% of pediatric and adult GERD patients fail standard doses of PPI and often undergo esophageal pH testing either on or off therapy. 14 Several factors contribu...

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First-line eradication forHelicobacter pylori-positive gastritis by esomeprazole-based triple therapy is influenced byCYP2C19genotype

Abstract: The results from this study suggest that there is no advantage to EPZ-based triple therapy on H. pylori eradication compared to other first-generation PPIs.

Cited by 27 publications

References 19 publications

Proton pump inhibitors: from CYP2C19 pharmacogenetics to precision medicine

Proton pump inhibitors: from CYP2C19 pharmacogenetics to precision medicine

Vonoprazan improves the efficacy of Helicobacter pylori eradication therapy with a regimen consisting of clarithromycin and metronidazole in patients allergic to penicillin

Association BetweenCYP2C19*17Alleles and pH Probe Testing Outcomes in Children With Symptomatic Gastroesophageal Reflux

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