Is the required therapeutic effect always achieved by racemic switch of proton-pump inhibitors?  

作　　者：Quan Zhou Xiao-Feng Yan Wen-Sheng Pan Su Zeng 

机构地区：[1]Department of Clinical Pharmacy, The 2nd Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, Zhejiang Province, China [2]Department of Gastroenterology, the 2nd Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, Zhejiang Province, China [3]Department of Pharmaceutical Analysis & Drug Metabolism, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, Zhejiang Province, China

出　　处：《World Journal of Gastroenterology》2008年第16期2617-2619,共3页世界胃肠病学杂志（英文版）

基　　金：Supported by Zhejiang Provincial Bureau of Education, No. 20070227;Zhejiang Medical Association, No.2007ZYC18;Association of Zhejiang Hospital Administration, No. 2007AZHA-KEB312

摘　　要：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.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.

关 键 词：Proton-pump inhibitors ENANTIOMER RACEMATE STEREOISOMERISM Racemic switch Pharmacokinetics PHARMACODYNAMICS Cytochrome P450 Genotype 

分 类 号：R9[医药卫生—药学]