[13C]-pantoprazole breath test to predict CYP2C19 phenotype and efficacy of a proton pump inhibitor, lansoprazole.
BACKGROUND
(13)CO(2) is produced on metabolism of (13)C-labelled-pantoprazole ([(13)C]-pantoprazole) by CYP2C19.


OBJECTIVE
To investigate whether the [(13)C]-pantoprazole breath test can predict CYP2C19 status and efficacy of proton pump inhibitors (PPIs) in Japanese.


METHODS
We classified 110 healthy volunteers as rapid metabolizers (RM), intermediate metabolizers (IM) or poor metabolizers (PM) of CYP2C19 by genotyping. Breath samples were collected at 10-min intervals for 60 min after dosing with 100 mg [(13)C]-pantoprazole. Changes in the carbon isotope ratios ((13)CO(2)/(12)CO(2)) in carbon dioxide in breath samples were measured and expressed as a delta-over-baseline (DOB) ratio ( per thousand). Of the 110 subjects, twenty-two randomly selected subjects underwent intragastric pH monitoring on day 7 of dosing with 30 mg of lansoprazole.


RESULTS
The DOB values of RMs were the highest and those of PMs the lowest of the three groups. Statistically significant differences were observed in the area-under-the-curve (AUC)(20-60 min) of DOB among the three groups. The mean 24-h intragastric pHs attained by lansoprazole 30 mg for 7 days were inversely correlated with the AUC(20-60 min) of DOB.


CONCLUSIONS
[(13)C]-pantoprazole breath test can easily estimate the individual activity of CYP2C19 and predict the efficacy of a PPI (i.e. lansoprazole). This test would be useful for individualized medicine with a PPI.
Furuta
T
T
Center for Clinical Research, Hamamatsu University School of Medicine, Hamamatsu, Japan. furuta@hama-med.ac.jp
Kodaira
C
C
Nishino
M
M
Yamade
M
M
Sugimoto
M
M
Ikuma
M
M
Hishida
A
A
Watanabe
H
H
Umemura
K
K
D053799:2-Pyridinylmethylsulfinylbenzimidazoles / Q000494:pharmacology*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000897:Anti-Ulcer Agents; D019540:Area Under Curve; D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism*; D001944:Breath Tests; D065731:Cytochrome P-450 CYP2C19; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D006801:Humans; D064747:Lansoprazole; D008297:Male; D008875:Middle Aged; D000077402:Pantoprazole; D054328:Proton Pump Inhibitors / Q000494:pharmacology*; D055815:Young Adult
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000897:Anti-Ulcer Agents; D004791:Enzyme Inhibitors; D054328:Proton Pump Inhibitors; D064747:Lansoprazole; D000077402:Pantoprazole; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19