A comparison of the acid‐inhibitory effects of esomeprazole and pantoprazole in relation to pharmacokinetics and CYP2C19 polymorphism

Abstract

SUMMARY BackgroundEsomeprazole and pantoprazole are metabolized in the liver and the polymorphic CYP2C19 enzyme is involved in that process. This genetic polymorphism determines fast (70% of Caucasians), intermediate (25-30% of Caucasians) and slow (2-5% of Caucasians) metabolism of PPIs.

Evaluation of the Pharmacokinetic Interaction between Lesogaberan (AZD3355) and Esomeprazole in Healthy Subjects

“…Although pharmacogenetic data were not collected in this study, CYP2C19 polymorphism has been shown to have minimal impact on the pharmacokinetics and pharmacodynamics of esomeprazole in homozygous and heterozygous CYP2C19 extensive metabolizers, [16] and the pharmacokinetic parameters of esomeprazole dosed alone in this study are similar to those previously reported. [15] Furthermore, the ratio and 95% CI of 4-bOH-cholesterol concentrations before and after treatment with lesogaberan indicated that lesogaberan does not induce CYP3A4.…”

Proton pump inhibitors: from CYP2C19 pharmacogenetics to precision medicine

“…Some reports have shown that variations in acid suppression are less significant when PPIs with less CYP2C19 dependent metabolism such as rabeprazole [27,47–49] or esomeprazole [50,52,53], are administered. CYP2C19 genotype dependent variation in median gastric PH was less for esomeprazole and rabeprazole compared to omeprazole and lansoprazole [51].…”

“…Specifically, rabeprazole is predominantly metabolized via nonenzymatic clearance. Another unique PK characteristic that distinguishes esomeprazole [26,53], is that it inhibits its own metabolism with repeated administration leading to higher PPI plasma levels with diminished genotype effect on acid suppression.…”

“…While some studies have documented genotype dependent differences in acid suppression and outcomes, others showed no relation between genotype and degree of acid suppression or outcomes for rabeprazole and esomeprazole [40,48,53,71,73,108]. This may be attributed in part to their lesser dependence on CYP2C19 metabolism, the higher potency of these PPIs [53,109,110], compared to other PPIs, lack of *17 testing [71], or combination of these factors, leading to diminished differences between the different CYP2C19 metabolizer phenotypes. Although the CYP2C19 genotype dependent increase of AUC in patients with PM phenotype may be less for PPIs that are minimally metabolized by CYP2C19, such as rabeprazole, the elevation in drug concentrations may still pose a risk of adverse events given its high potency.…”

Comparison of the effects of esomeprazole 40 mg, rabeprazole 20 mg, lansoprazole 30 mg, and pantoprazole 40 mg on intragastrıc pH in extensive metabolizer patients with gastroesophageal reflux disease

“…To date, studies have shown that extensive, intermediate, and poor metabolizers of CYP2C19 affect the metabolism of individual PPIs at different rates. In a study conducted by Hunfeld et al (27), the acid inhibitory effect and kinetics of pantoprazole were shown to be more influenced by the CYP2C19 genotype than that of esomeprazole. In another study by the same group (23), esomeprazole 40 mg was shown to provide a more effective and faster acid inhibitory effect than rabeprazole 20 mg.…”