CATH:D22:ZDIGE080XA.81 FF: ZU F9 E1: 66X2 5.11.2002 Review Digestion 2002;66:67–78 DOI: 10.1159/000065588 The Clinical Importance of Proton Pump Inhibitor Pharmacokinetics B.R. Yacyshyn a,b A.B.R. Thomson a a Department of Medicine, Division of Gastroenterology, University of Alberta, Edmonton, Canada; b Department of Medicine, Gastroenterology Section, Case Western Reserve University and Louis Stokes VA Hospitals, Cleveland, Ohio, USA Dr. Bruce Yacyshyn Division of Gastroenterology Case Western Reserve University and VA Medical Center Cleveland, OH 44106 (USA) E-Mail bruce.yacyshyn@med.va.gov ABC Fax + 41 61 306 12 34 E-Mail karger@karger.ch www.karger.com © 2002 S. Karger AG, Basel 0012–2823/02/0662–0067$18.50/0 Accessible online at: www.karger.com/journals/dig Key Words Proton pump inhibitors W Gastric ulcer W Duodenal ulcer W Reflux disease 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-sup- pressive effects. Available data indicate that PPIs appear to have similar potency on a milligram basis, and that omeprazole and lansoprazole are more frequently dou- ble dosed than pantoprazole. The lower propensity for double dosing with pantoprazole may also result in low- er medication acquisition costs and a reduction in physi- cian visits due to ineffective therapy with the standard dosing of these other agents. Copyright © 2002 S. Karger AG, Basel Introduction The widespread use and benefit of the proton pump inhibiting class of acid-suppressing drugs have been valu- able tools in the treatment of a range of upper gastrointes- tinal diseases. This work will review the pharmacology of these agents to better understand their optimal dosing and dose intervals for clinical use. This review was written in the light of prescription audit data demonstrating that double dosing is more common with omeprazole than with pantoprazole. Here we review the known literature about specific upper gastrointestinal diseases. The phar- macokinetics of proton pump inhibitors (PPIs) have been summarized elsewhere [1–6], but a few issues are relevant to this discussion (table 1). First, there is a substantial dif- ference in the bioavailability of these agents. Pantopra- zole and lansoprazole have the highest extent of absorp- tion. Pantoprazole has a bioavailability of 77% after the first dose, and this does not change after repeated dosing [10, 11], while that of lansoprazole is 80%. However, the bioavailability of omeprazole is 35% after the first dose, and it increases to about 60% with repeated doses [12, 13]. This fact indicates that, based solely on the pharma- cokinetics of these agents, it will take longer to reach the maximum therapeutic effect with omeprazole than with the other PPIs (except for esomeprazole – see below). The lower bioavailability of omeprazole, combined with a lower defined daily dose (DDD) (e.g., 20 mg for omepra-