Evaluation of Six Proton Pump Inhibitors As Inhibitors of Various Human Cytochromes P450: Focus on Cytochrome P450 2C19

2012 ◽  
Vol 40 (9) ◽  
pp. 1698-1711 ◽  
Author(s):  
Tatyana Zvyaga ◽  
Shu-Ying Chang ◽  
Cliff Chen ◽  
Zheng Yang ◽  
Ragini Vuppugalla ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Proton Pump Inhibitors ◽  
Proton Pump ◽  
Cytochromes P450 ◽  
Cytochrome P450 2C19

Abstract 3998: Proton Pump Inhibitors Effect on Clopidogrel Effectiveness: The Clopidogrel Medco Outcomes Study

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Ronald E Aubert ◽  
Robert S Epstein ◽  
J R Teagarden ◽  
Fang Xia ◽  
Jianying Yao ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Proton Pump Inhibitors ◽  
Proton Pump ◽  
Stent Placement ◽  
Adverse Outcomes ◽  
Coronary Artery Stent ◽  
Cytochrome P450 2C19 ◽  
Potential Impact ◽  
One Year ◽  
The One

Background: The anti-platelet properties of clopidogrel are thought to be activated by cytochrome P450 2C19. This isoenzyme is potently inhibited by the most commonly prescribed proton pump inhibitors (PPIs) and therefore may interfere with clopidogrel activation and its anti-platelet effects. Methods: We investigated the potential impact of PPIs on the effectiveness of clopidogrel to prevent coronary artery stent re-stenosis through a retrospective cohort study using the National Medco Integrated Database file, which covers approximately 19 million lives. We selected patients who underwent stent placement at sometime during a one-year period in 2005–2006, who started taking clopidogrel at the time of stent placement, and who were at least 80% compliant during the ensuing year (n=14,383). We followed these patients for the one-year incidence of major adverse CV events: hospitalization for stroke, MI, angina or CABG. We compared those who took clopidogrel alone (n=9862) vs. those who took clopidogrel with PPIs (n=4521), adjusting for baseline differences in age, gender and comorbidity. Results: Stent patients with no preceding CV events taking PPIs with clopidogrel showed a 32.5% incidence of a major CV event within one year vs. 21.2% of patients not taking PPIs (adjusted OR 1.79, CI 1.62–1.97). A more pronounced effect was seen among patients with a preceding CV event; 39.8% vs 26.2% (adjusted OR of 1.86, CI 1.63–2.12). Conclusions: Our findings suggest that the drug interaction between PPIs and clopidogrel may result in serious adverse outcomes within one year of therapy initiation, and further support investigations into the effects of cytochrome P450 2C19 genetic polymorphisms.

scholarly journals The Pharmacogenetics of Cytochrome P450 2C19 Enzymes - Effects on Clopidogrel and Proton Pump Inhibitors

2014 ◽  
Vol 6 (1) ◽  
pp. 33
Author(s):  
Yusmiati Yusmiati ◽  
Dewi Muliaty
Keyword(s):  
Cytochrome P450 ◽  
Proton Pump Inhibitors ◽  
Proton Pump ◽  
Platelet Reactivity ◽  
Active Form ◽  
Anti Platelet Therapy ◽  
Cytochrome P450 2C19 ◽  
Cyp2c19 Gene ◽  
Anti Platelet Drug ◽  
Clopidogrel Therapy

BACKGROUND: Cytochrome P450 (CYP) enzymes play important roles in human, including drug metabolism. CYP2 is the largest family of human CYP, with its sequence comprising almost one third of all CYP sequences, and responsible for the metabolism of approximately 2% of clinically administrated drugs. One of the most important enzymes in this family is the CYP2C19 enzyme. The CYP2C19 gene is polymorphic, and the variation is common especially in the Asian population.CONTENT: CYP2C19 is responsible for the metabolism of various drugs, including proton pump inhibitors (PPIs) such as omeprazole and lansoprazole, psychotropic drugs including diazepam and imipramine, anticonvulsants such as phenobarbital and mephenytoin. and the recently most studied the anti-platelet drug, clopidogrel, and many others. Drugs metabolized predominantly by this enzyme like clopidogrel and PPIs might be much affected by the genotype status of CYP2C19. Clopidogrel is a pro-drug requiring a group of enzymes to convert to its active form, particularly the CYP2C19. PPIs are metabolized to its inactive metabolites mainly by CYP2C19 in the liver. Some PPIs are inhibitor of CYP2C19 enzymes, and interaction of PPIs and clopidogrel has been widely studied.SUMMARY: The association of CYP2C19 genotypes with the plasma level of active clopidogrel and platelet reactivity in individual taking this drug is well-established. Although conflicting results still exist for the association of CYP2C19 genotypes to the clinical outcomes of clopidogrel therapy, this effect seems to be consistent in patients receiving clopidogrel for coronary stents. Due to the interaction of certain PPIs and clopidogrel, the use of PPIs other than omeprazole is recommended, especially for patients taking dual anti platelet therapy of clopidogrel and aspirin.KEYWORDS: pharmacogenetics, CYP2C19, proton pump inhibitors, clopidogrel

184 RELATIONSHIPS OF CYTOCHROME P450 2C19 GENOTYPES WITH PHARMACOKINETICS AND ANTI-H. PYLORI EFFICACY OF PROTON PUMP INHIBITORS

1996 ◽  
Vol 19 (5) ◽  
pp. 593
Author(s):  
Y. Tanigawara ◽  
T. Kita ◽  
N. Aoyama ◽  
K. Shirakawa ◽  
F. Komada ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Proton Pump Inhibitors ◽  
Proton Pump ◽  
Cytochrome P450 2C19 ◽  
H Pylori

scholarly journals Effect of proton pump inhibitors on cytochrome P450 2c19 activity in patients with gastroesophageal reflux disease.

2018 ◽  
Vol 96 (2) ◽  
pp. 164-167
Author(s):  
Yuliya S. Rabotyagova ◽  
I. L. Klyaritskaya ◽  
Anil Modak
Keyword(s):  
Enzyme Activity ◽  
Gastroesophageal Reflux Disease ◽  
Gastroesophageal Reflux ◽  
Proton Pump Inhibitors ◽  
Proton Pump ◽  
Reflux Disease ◽  
Non Invasive ◽  
Cytochrome P450 2C19 ◽  
Concomitant Medications

Patients with gastroesophageal reflux disease (GERD) are routinely prescribed one of the six proton pump inhibitors (PPI). All of these PPI are inhibitors of CYP2C19 enzyme to varying degrees. The phenotype 13C-pantoprazole breath test (Ptz-BT) was used to identify patients who are poor metabolizers (PM) and the extent of phenoconversion of CYP2C19 enzyme activity caused by four PPI (omeprazole, esomprazole pantoprazole and rabeprazole) in 54 newly diagnosed GERD patients prior to initiating randomly selected PPI therapy and 30 days after PPI therapy. The phenoconversion after 30 days of PPI therapy in GERD patients was statistically significant (p = 0.001) with omeprazole/esomeprazole (n = 27) strong CYP2C19 inhibitors, while there was no change in CYP2C19 enzyme activity (p = 0.8) with pantoprazole/rabeprazole (n = 27), weak CYP2C19 inhibitors. The rapid, in vivo, and non-invasive phenotype Ptz-BT can evaluate CYP2C19 enzyme activity. More importantly, it can identify GERD patients with low CYP2C19 enzyme activity (PM), caused by PPI or other concomitant medications, who would benefit from dose adjustments to maintain efficacy and avoid toxicity. The existing CYP2C19 genotype tests cannot predict the phenotype nor can it detect phenoconversion due to nongenetic factors.

scholarly journals Choice of protonic pump inhibitor with regard to multimorbidity: a focus on rabeprazol

2019 ◽  
pp. 34-42
Author(s):  
D. I. Trukhan ◽  
E. N. Degovtsov ◽  
A. L. Mazurov
Keyword(s):  
Coronary Heart Disease ◽  
Cytochrome P450 ◽  
Heart Disease ◽  
Gastrointestinal Tract ◽  
Proton Pump Inhibitors ◽  
Proton Pump ◽  
Gastroprotective Effect ◽  
Common Diseases ◽  
Wide Ph Range ◽  
Ph Range

Acid-related diseases occupy a leading place in the structure of the incidence of the gastrointestinal tract. One of the important aspects of studying them now is to consider them in combination with coronary heart disease, hypertension, diabetes, asthma and other common diseases and conditions. Proton pump inhibitors are currently the basis for the treatment of acid-related diseases. Although all PPIs are very effective, the antisecretory effects of various drugs of this class may differ in different patients, especially in the presence of comorbidities and comorbidities. The pharmacokinetics and metabolism of rabeprazole are significantly different from those of other IPPs. The clearance of rabeprazole is largely non-enzymatic and depends little on the functioning of the cytochrome P450 (CYP) 2C19 system, which determines the predictability of the effect of rabeprazole and its safety for patients taking several drugs at the same time. A distinctive effect of rabeprazole is the activation of rabeprazole in a wide pH range, the presence of a gastroprotective effect and anti-helicobacter activity.

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