Potent Gastric Acid Inhibition Over 24 Hours by 4-Times Daily Dosing of Esomeprazole 20 mg.
BACKGROUND
When administered at a standard dose, proton pump inhibitors (PPIs) do not always provide sufficient acid inhibition for all subjects, particularly in extensive metabolizers (EMs) of CYP2C19. Whether esomeprazole at a dose of 20 mg four times daily dosing (q.i.d.) can attain sufficient acid inhibition throughout 24 h in EMs remains unclear. We therefore investigated the efficacy of esomeprazole q.i.d. for acid inhibition.


METHODS
In a randomized cross-over design, 30 Helicobacter pylori-negative healthy young Japanese volunteers received esomeprazole at a dose of 20 mg two times a day (b.i.d.) or q.i.d. for 7 days. A pH monitoring was conducted before the trial as a control and on day 7 of both regimens.


RESULTS
Median pH values in the q.i.d. regimen were significantly higher than those with the b.i.d. regimen in EMs (b.i.d.: 5.3, q.i.d.: 6.6, p = 0.022), intermediate metabolizer (IM) (b.i.d.: 5.5, q.i.d.: 6.8, p = 0.005) and poor metabolizer (PM) (b.i.d.: 6.2, q.i.d.: 7.0, p = 0.047), respectively. Median pH with the b.i.d. regimen differed significantly by CYP2C19 genotypes (p = 0.004), but not the q.i.d. regimen (p = 0.384).


CONCLUSIONS
Esomeprazole q.i.d. achieved potent acid inhibition in all Helicobacter pylori-negative subjects, irrespective of CYP2C19 genotype, which might be one of the rescue regimens for patients' refractory to PPI treatment.
First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan.
Shu
S
Sahara
Mitsushige
M
Sugimoto
Takahiro
T
Uotani
Hitomi
H
Ichikawa
Mihoko
M
Yamade
Takuma
T
Kagami
Yasushi
Y
Hamaya
Moriya
M
Iwaizumi
Satoshi
S
Osawa
Ken
K
Sugimoto
Hiroaki
H
Miyajima
Takahisa
T
Furuta
D000328:Adult; D018592:Cross-Over Studies; D065731:Cytochrome P-450 CYP2C19 / Q000378:metabolism; D004334:Drug Administration Schedule; D064098:Esomeprazole / Q000008:administration & dosage*; D005260:Female; D005744:Gastric Acid / Q000378:metabolism; D005745:Gastric Acidity Determination; D005764:Gastroesophageal Reflux / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration / Q000187:drug effects; D007564:Japan; D008297:Male; D054328:Proton Pump Inhibitors / Q000008:administration & dosage*; D055815:Young Adult
D054328:Proton Pump Inhibitors; D065731:Cytochrome P-450 CYP2C19; D064098:Esomeprazole