Influence of different proton pump inhibitors on activity of cytochrome P450 assessed by [(13)C]-aminopyrine breath test

J Clin Pharmacol. 2012 Mar;52(3):432-9. doi: 10.1177/0091270010397728. Epub 2011 Mar 17.

Abstract

Aminopyrine is metabolized by cytochrome P450 (CYP) in the liver. The investigators evaluated influences of different PPIs on CYP activity as assessed by the [(13)C]-aminopyrine breath test ([(13)C]-ABT). Subjects were 15 healthy volunteers with different CYP2C19 status (5 rapid metabolizers [RMs], 5 intermediate metabolizers [IMs], and 5 poor metabolizers [PMs]). Breath samples were collected before and every 15 to 30 minutes for 3 hours after oral ingestion of [(13)C]-aminopyrine 100 mg on day 8 of each of the following regimens: control; omeprazole 20 mg and 80 mg, lansoprazole 30 mg, and rabeprazole 20 mg. Changes in carbon isotope ratios in carbon dioxide ((13)CO(2)/(12)CO(2)) in breath samples were measured by infrared spectrometry and expressed as delta-over-baseline (DOB) ratios (‰). Mean areas under the curve of DOB from 0 to 3 h (AUC(0-3h) of DOB) were significantly decreased by omeprazole 20 mg and lansoprazole 30 mg but not by rabeprazole 20 mg. Conversely, higher PPI dose (ie, omeprazole 80 mg) seemed to further decrease AUC(0-3h) of DOB in RMs but increased it in PMs. Omeprazole and lansoprazole at the standard doses inhibit CYP activity but rabeprazole does not, whereas high-dose omeprazole seems to induce CYPs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2-Pyridinylmethylsulfinylbenzimidazoles / pharmacokinetics
  • 2-Pyridinylmethylsulfinylbenzimidazoles / pharmacology
  • Aminopyrine / metabolism*
  • Anti-Ulcer Agents / pharmacokinetics
  • Anti-Ulcer Agents / pharmacology
  • Area Under Curve
  • Aryl Hydrocarbon Hydroxylases / genetics
  • Aryl Hydrocarbon Hydroxylases / metabolism*
  • Breath Tests
  • Carbon Isotopes
  • Cytochrome P-450 CYP2C19
  • Female
  • Genotype
  • Half-Life
  • Humans
  • Lansoprazole
  • Male
  • Omeprazole / pharmacokinetics
  • Omeprazole / pharmacology
  • Proton Pump Inhibitors / pharmacokinetics
  • Proton Pump Inhibitors / pharmacology*
  • Rabeprazole
  • Young Adult

Substances

  • 2-Pyridinylmethylsulfinylbenzimidazoles
  • Anti-Ulcer Agents
  • Carbon Isotopes
  • Proton Pump Inhibitors
  • Aminopyrine
  • Lansoprazole
  • Rabeprazole
  • Aryl Hydrocarbon Hydroxylases
  • CYP2C19 protein, human
  • Cytochrome P-450 CYP2C19
  • Omeprazole