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A comparative pharmacodynamic study of IY‐81149 versus omeprazole in patients with gastroesophageal reflux disease
Author(s) -
Periclou Antonia P.,
Goldwater Ronald,
Lee Seung Mok,
Park Dong Woo,
Kim Dong Yeon,
Do Cho Kil,
Boileau François,
Jung Won Tae
Publication year - 2000
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1067/mcp.2000.109155
Subject(s) - omeprazole , medicine , gastroenterology , reflux , crossover study , pharmacodynamics , pharmacokinetics , gastric acid , area under the curve , confidence interval , stomach , disease , pathology , placebo , alternative medicine
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 (pH median ), and the percent time in a 24‐hour interval in which the gastric pH was greater than 4 (t pH > 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), pH median , t pH > 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), pH median , t pH > 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. Clinical Pharmacology & Therapeutics (2000) 68 , 304–311; doi: 10.1067/mcp.2000.109155