A comparative pharmacodynamic study of IY-81149 versus omeprazole in patients with gastroesophageal reflux disease.
OBJECTIVE
To evaluate and compare the pharmacodynamic effects of IY-81149 and omeprazole on gastric pH in patients with gastroesophageal reflux disease.


METHODS
Sixty male and female volunteers with gastroesophageal reflux disease were enrolled in a double-blind, two-way, crossover, dose-ranging study. Subjects were randomized into three groups, with each group comparing the effect of one of three doses of IY-81149 (5, 10, or 20 mg) with 20 mg omeprazole. IY-81149 and omeprazole were administered once daily for 5 days. Continuous 24-hour pH measurements were performed before the first dose (baseline) and after the fifth dose in both periods. Gastric acid suppression was evaluated on the basis of the following parameters: AUC(0-24), median pH in a 24-hour interval (pHmedian), and the percent time in a 24-hour interval in which the gastric pH was greater than 4 (tpH > 4). The truncated AUC parameters AUC(0-8), AUC(8-16), and AUC(16-24) were also calculated. The effects of IY-81149 and omeprazole on gastric pH were compared by use of analyses of covariance. The dose-response relationship for IY-81149 was also evaluated.


RESULTS
There were no statistically significant differences between 5 mg IY-81149 and 20 mg omeprazole in terms of AUC(0-24), pHmedian, tpH, 4, AUC(0-8), and AUC(8-16). IY-81149, at 10 mg, produced a significantly greater gastric acid suppression than omeprazole on the basis of the values of AUC(0-24), pHmedian, tpH > 4, AUC(8-16), and AUC(16-24). Administration of 20 mg IY-81149 produced a significantly greater gastric acid suppression on the basis of all parameters. All doses of IY-81149 were more effective than omeprazole during 16 to 24 hours after the dose was administered.


CONCLUSIONS
Administration of 10 and 20 mg IY-81149 produced a statistically significantly greater and prolonged suppression of gastric pH than 20 mg omeprazole.
Periclou
A P
AP
MDS Harris, Vaudreuil, Québec, Canada. pericloua@labres.com
Goldwater
R
R
Lee
S M
SM
Park
D W
DW
Kim
D Y
DY
Cho
K D
KD
Boileau
F
F
Jung
W T
WT
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000284:Administration, Oral; D000328:Adult; D000704:Analysis of Variance; D000897:Anti-Ulcer Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D019540:Area Under Curve; D001562:Benzimidazoles / Q000493:pharmacokinetics / Q000494:pharmacology*; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005744:Gastric Acid / Q000378:metabolism; D005764:Gastroesophageal Reflux / Q000378:metabolism*; D006801:Humans; D006863:Hydrogen-Ion Concentration / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D009853:Omeprazole / Q000493:pharmacokinetics / Q000494:pharmacology*; D013454:Sulfoxides / Q000493:pharmacokinetics / Q000494:pharmacology*
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000897:Anti-Ulcer Agents; D001562:Benzimidazoles; D013454:Sulfoxides; C119615:ilaprazole; D009853:Omeprazole