CYP2C19 genotype and the PPIs – focus on rabeprazole

Lim, Paul; Goh, Khean‐Lee; Wong, Benjamin C Y

doi:10.1111/j.1440-1746.2005.04167.x

Cited by 41 publications

(34 citation statements)

References 33 publications

(61 reference statements)

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“…It is important to note that the degree to which CYP2C19 genotype impacts the PK and PD of PPIs depends on contribution of CYP2C19 to the metabolism of the individual PPI (Table 1). Specifically, CYP2C19 variation may have less impact on the metabolism of rabeprazole, for which the clearance is less dependent on CYP2C19 as it undergoes a nonenzymatic clearance [39]. …”

Section: Cyp2c19 and Ppi Pharmacogeneticsmentioning

confidence: 99%

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 Pharmacogeneticsmentioning

confidence: 99%

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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“…According to current US guidelines, PPIs are indicated with DAPT even in the absence of gastrointestinal symptoms [12]. All PPIs are, at least partly, metabolized by CYP2C19 [13,14]. Recent in vitro studies demonstrated that PPIs, particularly omeprazole, might alter the pharmacokinetics and decrease the antiplatelet effect of clopidogrel, which can be explained by inhibition of the CYP2C19-dependent activation of clopidogrel [15][16][17].…”

Section: Introductionmentioning

confidence: 99%

Combined clopidogrel and proton pump inhibitor therapy is associated with higher cardiovascular event rates after percutaneous coronary intervention: a report from the BASKET trial

Burkard¹,

Kaiser²,

Rocca³

et al. 2011

Journal of Internal Medicine

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). Combined clopidogrel and proton pump inhibitor therapy is associated with higher cardiovascular event rates after percutaneous coronary intervention: a report from the BASKET trial. J Intern Med 2012;271: 257-263.Objective. To investigate whether there is an increased risk of cardiac events with a combined therapy of clopidogrel and proton pump inhibitors (PPIs) after percutaneous coronary intervention (PCI).Design. In the BAsel Stent Kosten Effektivitäts Trial (BASKET), all patients undergoing PCI received 6 months of clopidogrel and were analysed for the use of PPI therapy. Endpoints were major adverse cardiac events (MACE), myocardial infarction (MI), death and target vessel revascularization (TVR) after 36 months.Results. Of 801 patients with available discharge medication data, 109 (14%) received PPIs. Patients who received PPIs were older (66.5 ± 10.5 vs. 63.3 ± 11.3 years, P = 0.006), more likely to be woman (80% vs. 69%, P = 0.009) and have a history of diabetes (29.6% vs. 17.3%, P = 0.002) or gastrointestinal ulcer disease (8.3% vs. 3.3%, P = 0.015) and more often received nonsteroidal anti-inflammatory drugs (7.3% vs. 2.2%, P = 0.003) and corticosteroids (11% vs. 3.6%, P = 0.001) but not aspirin (91.7% vs. 97%, P = 0.008) compared with those who did not receive PPIs. Patients who received PPI therapy had higher rates of MACE (30.3% vs. 20.8%, P = 0.027) and MI (14.7% vs. 7.4%, P = 0.01) but similar rates of death (9.2% vs. 7.4%, P = 0.51) and TVR (20.2% vs. 15.3%, P = 0.2) compared with those who did not. By multivariate analysis, diabetes (hazard ratio 1.83, 95% confidence interval 1.07-3.15) and PPI use (hazard ratio 1.88, 95% confidence interval 1.05-3.37) were the only independent risk factors for MI.Conclusion. In a real-world PCI population, the combination of PPIs and clopidogrel was associated with a doubling of MI rates after 3 years. Even after correction for confounding factors, concomitant PPI use remained an independent predictor of outcome emphasizing the clinical importance of this drug-drug interaction.

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“…Rabeprazole has a strong and stable effect to suppress gastric acid because it is less influenced by CYP2C19 genotype among the many available PPIs [21-23]. Thus, in this study, we examined the efficacy of vonoprazan compared with rabeprazole.…”

Section: Discussionmentioning

confidence: 99%

Vonoprazan is Superior to Rabeprazole for Healing Endoscopic Submucosal Dissection: Induced Ulcers

Yamasaki¹,

Yoshio

Muramatsu

et al. 2018

Digestion

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Background and Aims: Endoscopic submucosal dissection (ESD) is a well-established minimally invasive treatment for early gastric cancer. To heal ESD-induced ulcers, we commonly prescribe proton pump inhibitors (PPIs). Vonoprazan is our new choice, which is reported to have a stronger and longer acid inhibitory effect than existing PPIs. Here, we aimed to evaluate the efficacy of vonoprazan for healing ESD-induced ulcers compared with rabeprazole. Methods: We reviewed 190 patients who underwent ESD before and after we switched the acid secretion inhibitor from rabeprazole to vonoprazan. We evaluated scarring and reduction rates at 4 weeks after ESD. Results: Scarring rates were not different between vonoprazan and rabeprazole (31.7 vs. 18.9%; p = 0.07). However, for ulcers ≤35 mm, vonoprazan was superior to rabeprazole (42.2 vs. 19.2%; p < 0.05). Reduction rates were superior for vonoprazan compared with rabeprazole (93.0 vs. 90.4%; p < 0.05). In multivariate analysis, vonoprazan was superior to rabeprazole for ulcer scarring (OR 2.21; p < 0.05), and ulcer location in the lower-third of the stomach had higher risk of incomplete scarring (OR 0.37; p < 0.05). Conclusion: Vonoprazan was superior to rabeprazole for healing ESD-induced ulcers.

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CYP2C19 genotype and the PPIs – focus on rabeprazole

Cited by 41 publications

References 33 publications

Proton pump inhibitors: from CYP2C19 pharmacogenetics to precision medicine

Proton pump inhibitors: from CYP2C19 pharmacogenetics to precision medicine

Combined clopidogrel and proton pump inhibitor therapy is associated with higher cardiovascular event rates after percutaneous coronary intervention: a report from the BASKET trial

Vonoprazan is Superior to Rabeprazole for Healing Endoscopic Submucosal Dissection: Induced Ulcers

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