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Dig Dis Sci (2007) 52:28262832 DOI 10.1007/s10620-006-9643-x
ORIGINAL PAPER
Acid-Suppressive Effects of Various Regimens of Omeprazole in Helicobacter pylori-Negative CYP2C19 Homozygous Extensive Metabolizers: Which Regimen Has the Strongest Effect?
Tomohiko Shimatani Tomoko Kuroiwa Mutsuko Moriwaki Jing Xu Susumu Tazuma Masaki Inoue
Received: 11 August 2006 / Accepted: 9 October 2006 / Published online: 5 April 2007
C
Springer Science+Business Media, LLC 2007
Abstract To achieve more potent and long-lasting acid suppression, omeprazole was administered for 7 days in 5 regimens: 10, 20, and 40 mg once daily (od), and 10 and 20 mg twice daily (bid), in 7 healthy Helicobacter pylori-negative CYP2C19 homozygous extensive metabolizers, and intragastric pH was continuously measured. The median intragastric pH and percent time pH > 4.0 for 24 hours increased dose dependently with 10, 20, and 40 mg od. Ten and 20 mg bid wre comparable to 20 and 40 mg od, respectively. Concerning percent time pH > 4.0 in the nighttime (20:008:00 hours), 20 mg bid was signicantly superior to 40 mg od (P < .05). In 4 of the 5 regimens, all 7 subjects had nocturnal acid breakthrough, whereas with 20 mg bid it occurred in only 3. We concluded that, considering nighttime acid suppression, omeprazole 20 mg bid had the strongest effect.
Keywords Omeprazole . CYP2C19 . Homozygous extensive metabolizer . Intragastric pH . Divided dose
T. Shimatani ([envelopeback]) S. Tazuma Department of General Medicine, Hiroshima University Hospital, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan
T. Kuroiwa M. Moriwaki J. Xu Department of Geriatric Health Sciences, Graduate School of Health Sciences, Hiroshima University,1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan
M. Inoue Department of Internal Medicine, Hiroshima Prefectural Akitsu Hospital, 4388 Mitsu, Akitsu-cho, Higashi-Hiroshima 729-2402, Japan
Introduction
Omeprazole, a proton pump inhibitor (PPI), is a substituted benzimidazole that inhibits parietal cell H+, K+ ATPase [1, 2], thus causing potent and long-lasting inhibition of the terminal step in gastric acid secretion [1]. In many countries omeprazole 20 or 40 mg once daily (od) is approved for use as initial therapy for gastroesophageal reux disease (GERD), and 10 or 20 mg od is the dose often used for maintenance therapy for GERD. Satisfactory clinical outcomes have been reported [37].
In patients with high-grade GERD and Barrett esophagus, exposure of the esophagus...