A46 THE IMPACT OF CYP2C19 POLYMORPHISM ON PROTON PUMP INHIBITORS DOSING: A RETROSPECTIVE ANALYSIS
Bibliographic record
Abstract
Proton pump inhibitors (PPIs) are used in a wide spectrum of gastrointestinal disorders. They undergo significant metabolism by the main enzyme Cytochrome P450 2C19 (CYP2C19). Genetic variation in this enzyme influences the pharmacokinetics of all PPIs. Despite the different challenges with implementing pharmacogenetics-guided therapy in clinical practice, CYP2C19 pharmacogenomics testing is currently available at London Health Sciences Centre (LHSC) as we recognize the major role it plays in drug responses and interactions in different clinical scenarios. However, its role in PPIs response in different gastrointestinal disorder needs further studies. To investigate the frequency of CYP2C19 polymorphism in our patient population in a tertiary care center in London, Ontario, and its correlation with high and standard PPI dosing. Standard dose was defined as 30 mg per day for lansoprazole and 40 mg per day for pantoprazole. The high dose was defined as a dose that is double the standard dose. A retrospective chart review was performed of all adult patients who were on CYP-dependent PPIs (lansoprazole and pantoprazole) and underwent CYP2C19 genotype testing in our lab for different indications from January 2010 to July 2017. Statistical testing was conducted to compare high PPI dose group with standard PPI dose group. The primary outcome was to describe the correlation between CYP2C19 genotype and PPI dose. 79 genotyped patients were included in this interim analysis, of whom 22 patients (27.8%) were on high dose PPI and 57 (72.2%) were on standard dose. There was no statistically significant difference between the high dose group and standard dose group in age, gender or BMI. The high dose group patients were more likely to have a previous history of PUD (p<0.001), erosions (p<0.001) and UGIB (p=0.002). Extensive metabolizers (EM) was the most common CYP2C19 phenotype in both groups (81.8% vs. 70.2%; p=0.29) with intermediate metabolizers (IM), poor metabolizers (PM) and ultra-rapid metabolizers (UM) identified more in the standard dose group (9.1% vs. 19.3%, p=0.27; 4.5% vs. 5.4%, p=0.9; 4.5% vs. 5.4%, p=0.9; respectively). Patients in the high dose group experienced improvement in their PUD and UGIB more than the standard dose group patients (p=0.003 and p=0.01, respectively). IM and PM patients were found to be on standard dose PPIs more often but this was not statistically significant. In this interim analysis, there was no statistically significant difference in PPI dosing among CYP2C19 different phenotypes. CYP2C19 genotype testing might have a role in PPI dosing. Future prospective randomized controlled trials are needed to further identify that role. A larger sample size will be presented in the Canadian Digestive Disease Week. None
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.003 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.002 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".