Letters To The Editor
Copyright ©2008 The WJG Press and Baishideng. All rights reserved.
World J Gastroenterol. Apr 28, 2008; 14(16): 2617-2619
Published online Apr 28, 2008. doi: 10.3748/wjg.14.2617
Is the required therapeutic effect always achieved by racemic switch of proton-pump inhibitors?
Quan Zhou, Xiao-Feng Yan, Wen-Sheng Pan, Su Zeng
Quan Zhou, Xiao-Feng Yan, Department of Clinical Pharmacy, The 2nd Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, Zhejiang Province, China
Wen-Sheng Pan, Department of Gastroenterology, the 2nd Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, Zhejiang Province, China
Su Zeng, Department of Pharmaceutical Analysis & Drug Metabolism, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, Zhejiang Province, China
Author contributions: Zhou Q and Zeng S contributed equally to this work; Zhou Q and Pan WS put forward the viewpoint and designed the research; Zhou Q, Yan XF and Zeng S performed the literature review and data analysis/ interpretation; and Zhou Q and Zeng S wrote the paper.
Correspondence to: Quan Zhou, Associate Professor, Department of Clinical Pharmacy, The 2nd Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang 310009, China. zhouquan142602@zju.edu.cn
Telephone: +86-571-87783891
Fax: +86-571-87213864
Received: January 11, 2008
Revised: February 28, 2008
Published online: April 28, 2008
Abstract

Many of the drugs currently used in medical practice are racemates. The enantiomers of a racemic drug differ in pharmacodynamics and/or pharmacokinetics, thus in some cases it is preferable to develop pure enantiomers by racemic switch. In a recent study by Pai et al, dexrabeprazole [R(+)-rabeprazole] (10 mg) was found to be more effective than rabeprazole (20 mg) in the treatment of gastroesophageal reflux disease. We read with great interest in this study and discussed whether such racemic switch would be applicable to other proton-pump inhibitors (PPIs). A literature review indicates that stereoselective pharmacokinetics, rather than stereoselective pharmacological activity, is the main cause of differences in clinical efficacy between pure enantiomer and racemic PPI. Racemic switches of PPI provide the therapeutic advantages such as reducing metabolic load on the body, simplifying pharmacokinetics, providing benefit to the non-responders to standard dose of racemate, more homogenous response to treatment and better efficacy with equal safety. Further studies in quantitative structure-activity relationships (QSARs) are needed to address the fact that the preferred enantiomer of PPI is not always in the same absolute configuration, i.e., S-form is for omeprazole, pantoprazole and tenatoprazole whereas R-form is for lansoprazole and rabeprazole.

Keywords: Proton-pump inhibitors; Enantiomer; Racemate; Stereoisomerism; Racemic switch; Pharmacokinetics; Pharmacodynamics; Cytochrome P450; Genotype