Update on the Pharmacogenomics of Proton Pump Inhibitors: Abstract and Introduction

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Update on the Pharmacogenomics of Proton Pump Inhibitors
Krisztina Hagymási; Katalin Müllner; László Herszényi; Zsolt Tulassay

Authors and Disclosures

Posted: 07/08/2011; Pharmacogenomics. 2011;12(6):873-888. © 2011 Future Medicine Ltd.

Abstract and Introduction
Abstract

Proton pump inhibitors (PPIs) are widely used for the treatment of gastroesophageal reflux disease as well as other acid-related disorders. PPIs are metabolized primarily via the CYP2C19 and CYP3A4 isoenzymes; their activity is influenced both by exogenous and endogenous (pharmacogenetic) factors. The CYP2C19 polymorphism affects the metabolism of PPIs, causing large individual pharmacokinetic variations. Differences in the CYP2C19-mediated metabolism can produce marked interpatient variability in acid suppression, in drug-interaction potential and in clinical efficacy. Understanding the pharmacokinetic properties of PPIs and examining the pharmacogenetic alterations may help clinicians optimize PPI therapy and administer individual treatment, especially to nonresponder patients with gastroesophageal reflux disease or ulcer or after failed eradication therapy.
Introduction

Medication response rates are far from being optimal, since they have been estimated to range between 30 and 60%. Reported adverse drug events have increased from 30,000 to 90,000 events from 1998 to 2005. The outcome of certain drug therapies depends on the genetic background of the patient. Indeed, knowledge of the genetic background may result in improved treatment responses as well as significant reductions in adverse drug events.[1]

Proton pump inhibitors (PPIs) are popular and prevalent medications, owing to their proven efficacy and safety. Omeprazole, lansoprazole, pantoprazole, rabeprazole, esomeprazole and tenatoprazole are used to treat acid-related disorders: gastroesophageal reflux disease (GERD), Barret's esophagus, peptic ulcer disease, Zollinger–Ellison syndrome, gastrinomas and esophagitis/gastritis.[2] Sales of PPIs are in excess of $10 billion per year.[3]

Both pharmacokinetic and pharmacodynamic differences can be observed among the different PPI, which might influence their clinical application. However, the same PPI can have widely different therapeutic effects on individuals. There are either genetic reasons or drug interactions that cause these differences.

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