Bibliographic record
Abstract
Cytochrome P450 (CYP) 2C19 mediates the major metabolic transformations of the proton pump inhibitors (PPIs) omeprazole, pantoprazole, lansoprazole, esomeprazole, and rabeprazole. Genetic polymorphism of CYP2C19 can lead to significant phenotypic variation in the activity of this isoenzyme and thus in the metabolism of PPIs. We systematically reviewed the pharmacogenetic studies of PPIs with respect to the effects of CYP2C19 polymorphism on the clinical outcomes of PPI therapy. We searched MEDLINE (January 1966-August 2002) and EMBASE (January 1988-August 2002) for English-language articles on the pharmacogenetics of PPIs; the search was supplemented by a bibliographic review of all relevant articles. Seventeen pertinent citations were identified, and the quality (level) of evidence for each was categorized according to the rating scale of the United States Preventive Services Task Force. We found that the relationship between CYP2C19 genetic polymorphism and clinical outcomes after PPI therapy has not yet been clearly delineated. Virtually all pharmacogenetic studies of PPIs have been performed in Japanese men; thus, the clinical relevance of CYP2C19 genetic polymorphism in non-Asian patients and women is unknown. Differences among dual- and triple-therapy drug regimens make it difficult to compare H. pylori eradication studies and assess their applicability to current practice patterns. Drug adherence, a pivotal factor in the success of eradication therapy, was addressed in only four trials. Future directions for research include performing more studies with larger sample sizes, particularly in non-Asian populations and women; measuring plasma PPI concentrations to directly correlate H. pylori infection and ulcer cure rates with plasma drug availability; expanding the study population to patients with gastroesophageal reflux disease; and exploring the influence of CYP3A4 in the success or failure of PPI therapy. Although CYP2C19 genotyping is currently only a research instrument, it may be a valuable clinical tool in select patients to ensure optimal PPI therapy.
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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 | 0.005 | 0.028 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.009 | 0.004 |
| Bibliometrics | 0.010 | 0.014 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.002 | 0.002 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.002 | 0.001 |
| Insufficient payload (model declined to judge) | 0.006 | 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".