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      About Digestion: 3.2 Impact Factor I 6.4 CiteScore I 0.914 Scimago Journal & Country Rank (SJR)

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      The Clinical Importance of Proton Pump Inhibitor Pharmacokinetics

      review-article
      a,b , a
      Digestion
      S. Karger AG
      Proton pump inhibitors, Gastric ulcer, Duodenal ulcer, Reflux disease

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          Abstract

          Achieving the optimal clinical response for patients with upper gastrointestinal peptic disease is important. This response depends on the pathology treated as well as on the choice of proton pump inhibitor. Here, we identify factors in specific disease therapy and proton pump inhibitor (PPI) pharmacokinetic and pharmacodynamic characteristics that help us achieve this goal. These include differences in PPI bioavailability and acid-suppressive effects. Available data indicate that PPIs appear to have similar potency on a milligram basis, and that omeprazole and lansoprazole are more frequently double dosed than pantoprazole. The lower propensity for double dosing with pantoprazole may also result in lower medication acquisition costs and a reduction in physician visits due to ineffective therapy with the standard dosing of these other agents.

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          Most cited references9

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          The effects of oral doses of lansoprazole and omeprazole on gastric pH.

          We compared gastric pH values after therapeutic doses of lansoprazole and omeprazole in 17 healthy adult men. The pharmacokinetics of the two drugs were studied. A three-way crossover design compared the effects on gastric pH of 15 and 30 mg lansoprazole and 20 mg omeprazole--each given once daily for 5 days. Ambulatory 24-h intragastric pH levels were measured before dosing, after the first and fifth doses in each period, and 15 days after each dosing period. A positive relationship between the lansoprazole or omeprazole area under the curve (AUCs) and the 24-h mean pH values was found for each regimen. No differences in maximum concentration (Cmax) and AUC were noted from day 1 to day 5 for the two lansoprazole doses. With omeprazole, both Cmax and AUC levels were greater on day 5 than on day 1. All three regimens increased 24-h mean gastric pH, although 30 mg lansoprazole had the most significant effect. The percentage of time that gastric pH was >3, >4, and >5 was also significantly higher with 30 mg lansoprazole. All three regimens were associated with reversible elevations of serum gastrin, which more than doubled at some points. No clinically significant adverse events were documented.
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            Decreasing oesophageal acid exposure in patients with GERD: a comparison of rabeprazole and omeprazole.

            Rabeprazole has been shown to be more potent and faster than other proton pump inhibitors in in vitro studies and highly effective in decreasing oesophageal acid exposure in patients with gastro-oesophageal reflux disease (GERD). This study was a multicentre, double-blind, placebo-controlled, randomized, parallel-group comparison of three active treatment regimens utilizing two different proton pump inhibitors, or placebo, administered over 7 days in patients with GERD. Eighty-two patients with symptomatic GERD were given placebo, rabeprazole 10 mg b.d., rabeprazole 20 mg o.m., or omeprazole 20 mg o.m. for 7 days. Twenty-four hour oesophageal pH monitoring was performed at baseline and repeated at the conclusion of the treatment period. At the end of study, the percentage time (mean +/- s.d.) with pH < 4 over a 24-h period was significantly decreased by the three active regimens but without significant difference between them (9.27 +/- 4.77; 2.53 +/- 4.27; 2.02 +/- 1.71 and 2.91 +/- 4.06 for placebo, rabeprazole 10 mg b.d., rabeprazole 20 mg o.m. and omeprazole 20 mg o.m., respectively). Acid exposure was normalized in 90% of patients treated with rabeprazole 10 mg b.d., 95% treated with rabeprazole 20 mg o.m., 78% treated with omeprazole 20 mg o.m., and only 9.5% of patients treated with placebo. Both rabeprazole and omeprazole were well-tolerated. Although rabeprazole 20 mg o.m. showed greater activity numerically, this study demonstrates that rabeprazole 10 mg b.d. and 20 mg o.m. are equivalent to omeprazole 20 mg o.m. in decreasing oesophageal acid exposure.
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              Relative efficacies of gastric proton pump inhibitors: their clinical and pharmacological basis.

              The present review will verify by intra-study rank orders, and their comparison between studies, that the different gastric proton pump inhibitors (PPIs) display similar dose-response relationships with similar potencies and efficacies on a milligram basis, i.e., at the same milligram doses. This is in line with their basic pharmacology which suggests that, primarily, the serum AUCs of the free pro-drugs and their chemical activation half lives at pH 1 relative to their serum elimination half lives determine the efficacies of PPIs. According to the literature, these drug characteristics are similar for all PPIs. Although PPIs have been introduced into the therapy of acute peptic ulcer disease at different daily, oral doses of 20 mg (omeprazole and rabeprazole), 30 mg (lansoprazole) and 40 mg (pantoprazole), the data suggest that the optimal dose of lansoprazole, omeprazole and pantoprazole, with respect to the acute treatment of peptic ulcers and moderate to severe gastroesophageal reflux disease (GERD), is about 30-40 mg daily. The data base of rabeprazole appears to be too small at present to make any definite statement. Lower daily doses of the PPIs of about 15-20 mg are sufficient in less severe cases of GERD and in maintenance therapy. It appears that different dose recommendations were based on different strategies to balance optimal drug dosage and safety, rather than on real differences in milligram-related efficacies.
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                Author and article information

                Journal
                DIG
                Digestion
                10.1159/issn.0012-2823
                Digestion
                S. Karger AG
                0012-2823
                1421-9867
                2002
                2002
                20 November 2002
                : 66
                : 2
                : 67-78
                Affiliations
                aDepartment of Medicine, Division of Gastroenterology, University of Alberta, Edmonton, Canada; bDepartment of Medicine, Gastroenterology Section, Case Western Reserve University and Louis Stokes VA Hospitals, Cleveland, Ohio, USA
                Article
                65588 Digestion 2002;66:67–78
                10.1159/000065588
                12428065
                f1c42e4f-e5ef-49b4-b854-7463e93dee36
                © 2002 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                History
                : 07 June 2001
                : 04 March 2002
                Page count
                Figures: 4, Tables: 3, References: 93, Pages: 12
                Categories
                Review

                Oncology & Radiotherapy,Gastroenterology & Hepatology,Surgery,Nutrition & Dietetics,Internal medicine
                Proton pump inhibitors,Gastric ulcer,Duodenal ulcer,Reflux disease

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