title: Influence of different proton pump inhibitors on activity of cytochrome P450 assessed by [(13)C]-aminopyrine breath test.
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.
authors.affiliation: First Department of Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, 431-3192, Japan.
authors.forename: Chise
authors.initials: C
authors.lastname: Kodaira
authors.forename: Shinya
authors.initials: S
authors.lastname: Uchida
authors.forename: Mihoko
authors.initials: M
authors.lastname: Yamade
authors.forename: Masafumi
authors.initials: M
authors.lastname: Nishino
authors.forename: Mutsuhiro
authors.initials: M
authors.lastname: Ikuma
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Namiki
authors.forename: Mitsushige
authors.initials: M
authors.lastname: Sugimoto
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Watanabe
authors.forename: Akira
authors.initials: A
authors.lastname: Hishida
authors.forename: Takahisa
authors.initials: T
authors.lastname: Furuta
mesh_terms: D053799:2-Pyridinylmethylsulfinylbenzimidazoles / Q000493:pharmacokinetics / Q000494:pharmacology; D000632:Aminopyrine / Q000378:metabolism*; D000897:Anti-Ulcer Agents / Q000493:pharmacokinetics / Q000494:pharmacology; D019540:Area Under Curve; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics / Q000378:metabolism*; D001944:Breath Tests; D002247:Carbon Isotopes; D065731:Cytochrome P-450 CYP2C19; D005260:Female; D005838:Genotype; D006207:Half-Life; D006801:Humans; D064747:Lansoprazole; D008297:Male; D009853:Omeprazole / Q000493:pharmacokinetics / Q000494:pharmacology; D054328:Proton Pump Inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology*; D064750:Rabeprazole; D055815:Young Adult
chemical_list: D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000897:Anti-Ulcer Agents; D002247:Carbon Isotopes; D054328:Proton Pump Inhibitors; D000632:Aminopyrine; D064747:Lansoprazole; D064750:Rabeprazole; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D009853:Omeprazole