A46 THE IMPACT OF CYP2C19 POLYMORPHISM ON PROTON PUMP INHIBITORS DOSING: A RETROSPECTIVE ANALYSIS
Notice bibliographique
Résumé
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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Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,001 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,001 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».