Effect of concomitant dosing of famotidine with lansoprazole on gastric acid secretion in relation to CYP2C19 genotype status.
BACKGROUND
Famotidine increases Helicobacter pylori-eradication rates by a triple lansoprazole/amoxicillin/clarithromycin therapy in patients with the rapid extensive metabolizer genotype of CYP2C19.


OBJECTIVE
To determine the effect of famotidine on the gastric acid inhibition by lansoprazole in relation to CYP2C19 genotypes.


METHODS
Twenty healthy volunteers with different CYP2C19 genotypes--consisting of six rapid extensive metabolizers, nine intermediate metabolizers and five poor metabolizers--underwent three 7-day courses with placebo, lansoprazole 30 mg twice daily, and lansoprazole 30 mg twice plus famotidine 20 mg twice daily. Lansoprazole was dosed after breakfast and dinner. Famotidine was dosed after lunch and at bedtime. Intragastric pH monitoring was performed for 24 h on day 7 of each course.


RESULTS
With placebo, no difference was observed in intragastric pH profiles among the three CYP2C19 genotype groups. With lansoprazole 30 mg twice daily, the median of 24-h intragastric pH in poor metabolizers (6.1) was significantly higher than those of rapid extensive metabolizers (4.5) and intermediate metabolizers (5.0), respectively (P = 0.0176 and 0.0388), whereas with lansoprazole 30 mg twice and famotidine 20 mg twice daily, the medians were 5.4, 5.7, and 6.1, respectively (not significant).


CONCLUSIONS
Acid inhibition by lansoprazole was influenced by CYP2C19 genotype status. This influence was offset by the concomitant use of famotidine.
Furuta
T
T
First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan. furuta@hama-med.ac.jp
Shirai
N
N
Sugimoto
M
M
Nakamura
A
A
Okudaira
K
K
Kajimura
M
M
Hishida
A
A
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000328:Adult; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D018592:Cross-Over Studies; D065731:Cytochrome P-450 CYP2C19; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004347:Drug Interactions; D015738:Famotidine / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D005744:Gastric Acid / Q000378:metabolism*; D005838:Genotype; D006801:Humans; D006863:Hydrogen-Ion Concentration; D064747:Lansoprazole; D008297:Male; D006899:Mixed Function Oxygenases / Q000235:genetics*; D009853:Omeprazole / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000897:Anti-Ulcer Agents; D004338:Drug Combinations; D064747:Lansoprazole; D015738:Famotidine; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D009853:Omeprazole