Monitoring Cytochrome P-450 Activity During Rabeprazole Treatment in Patients with Gastresophageal Reflux Disease

Abstract

Proton pump inhibitors (PPIs) are the cornerstone in the treatment of gastresophageal reflux disease (GORD). PPIs are metabolized by the hepatic cytochrome P-450 enzymes (CYP-450). Rabeprazole is a PPI whose metabolism shows fewer interactions compared to other PPIs. In this study we evaluated the influence of rabeprazole administration on hepatic CYP-450 activity as measured by the (13)C-aminopyrine breath test ((13)C-ABT) in a group of patients with GORD. (13)C-ABT was performed on five GORD patients both before and after 1 week of rabeprazole administration (20 mg, b.i.d.). Pretreatment (13)C-ABT results were compared to posttreatment results. Pre- and posttreatment (13)C-ABT results for patients were compared to those obtained in five controls who did the test twice, with a 1-week interval in between. Before treatment, the (13)C-ABT results for the GORD patients did not significantly differ from those of healthy subjects. After treatment, we observed no significant modification of the (13)C-ABT in GORD patients compared to pretreatment values ((13)C-ABT %dose/hr, 10.56+/-1.31 versus 11.17+/-0.88; (13)C-ABT %cumulative dose, 8.08+/-1.11 versus 8.34+/-0.56). Posttreatment (13)C-ABT results were not significantly different from those obtained in controls at weekly repetition of the test. In patients with GORD, 1-week, full-dose rabeprazole does not display any significant interactions with CYP-450 activity.

Influence of Different Proton Pump Inhibitors on Activity of Cytochrome P450 Assessed by [13C]‐Aminopyrine Breath Test

“…These investigators performed [ 13 C]-ABT during rabeprazol in patients with gastroesophageal reflux disease and showed that 1-week, full-dose rabeprazole does not display any significant interactions with CYPs. 25 The present study reconfirmed that rabeprazole has little inhibitory effect on CYP activity as assessed by [ 13 C]-ABT. Our study also demonstrated that omeprazole and lansoprazole inhibit CYP activity.…”

“…Giannini et al 24 also reported in another study that rabeprazole did not inhibit CYP activity in eradication of H pylori with antimicrobial agents. These investigators performed [ 13 C]‐ABT during rabeprazol in patients with gastroesophageal reflux disease and showed that 1‐week, full‐dose rabeprazole does not display any significant interactions with CYPs 25 . The present study reconfirmed that rabeprazole has little inhibitory effect on CYP activity as assessed by [ 13 C]‐ABT.…”

A study of 4‐ and 7‐day triple therapy with rabeprazole, high‐dose levofloxacin and tinidazole rescue treatment for Helicobacter pylori eradication

“…In fact, the peculiar pharmacokinetics and pharmacodynamics of rabeprazole allow a faster onset of action, and more rapid inhibition of proton pumps than other PPIs, 32, 33 thus making this drug more suitable for short‐term eradication treatment because both fast activation and rapid onset of gastric acid suppression are especially needed in short‐term therapy. Moreover, rabeprazole has relevant in vitro antimicrobial activity, 34, 35 and its administration does not seem to interfere with cytochrome P‐450 activity 36, 37 . This is especially important as in this study, and as happens in everyday clinical practice, approximately half of the patients were on co‐medication, and in this setting the occurrence of drug–drug interactions is more likely.…”

Acid inhibition effect of ilaprazole on Helicobacter pylori‐negative healthy volunteers: An open randomized cross‐over study

“…Benzimidazole-based PPIs are often challenged by having their effects influenced by individual hepatic CYP activity. 15,16 Unlike esomeprazole or lansoprazole, 17 omeprazole is more dependent on the CYP2C19 genotype. 18 The current study also shows less effect by CYP2C19 on ilaprazole than on omeprazole.…”