Literature DB >> 15080762

Single-enantiomer drugs: elegant science, disappointing effects.

Peter Mansfield1, David Henry, Anne Tonkin.   

Abstract

Most new drugs are marketed as single enantiomers but many older agents are still available in racemic form. As these drugs reach the end of their patent life manufacturers become interested in marketing single enantiomer equivalents. This is called 'chiral switching' and it has been claimed that it will bring clinical benefits in terms of improved efficacy, more predictable pharmacokinetics or reduced toxicity. We reviewed the clinical evidence and prices for three recently marketed single enantiomer versions of widely used racemic drugs: escitalopram, esomeprazole and levosalbutamol. Claims of increased efficacy were based on comparisons of non-equivalent doses and any advantages seemed small and clinically unimportant. Prices of esomeprazole and levosalbutamol were higher than their racemic alternatives and we predict that these prices will remain high despite the market presence of generic versions of the racemates. Patent protection and a perception of superiority based on promotion rather than evidence will maintain price premiums for single enantiomer drugs that are not justified on the basis of clinical performance.

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Year:  2004        PMID: 15080762     DOI: 10.2165/00003088-200443050-00002

Source DB:  PubMed          Journal:  Clin Pharmacokinet        ISSN: 0312-5963            Impact factor:   6.447


  18 in total

Review 1.  Chiral switches.

Authors:  G T Tucker
Journal:  Lancet       Date:  2000-03-25       Impact factor: 79.321

Review 2.  Stereoselective pharmacokinetics and pharmacodynamics of anti-asthma agents.

Authors:  Majid Vakily; Reza Mehvar; Dion Brocks
Journal:  Ann Pharmacother       Date:  2002-04       Impact factor: 3.154

Review 3.  The pharmaceutical industry as a medicines provider.

Authors:  David Henry; Joel Lexchin
Journal:  Lancet       Date:  2002-11-16       Impact factor: 79.321

Review 4.  Stereochemistry and drug efficacy and development: relevance of chirality to antidepressant and antipsychotic drugs.

Authors:  Glen B Baker; Trevor I Prior
Journal:  Ann Med       Date:  2002       Impact factor: 4.709

5.  Levalbuterol has not been established to have therapeutic advantage over racemic albuterol.

Authors:  Michael J Asmus; Leslie Hendeles; Miles Weinberger; Richard C Ahrens; Hans Bisgaard; Jan Lötvall; Paul M O'Byrne; Donald W Cockcroft
Journal:  J Allergy Clin Immunol       Date:  2002-08       Impact factor: 10.793

6.  Esomeprazole improves healing and symptom resolution as compared with omeprazole in reflux oesophagitis patients: a randomized controlled trial. The Esomeprazole Study Investigators.

Authors:  P J Kahrilas; G W Falk; D A Johnson; C Schmitt; D W Collins; J Whipple; D D'Amico; B Hamelin; B Joelsson
Journal:  Aliment Pharmacol Ther       Date:  2000-10       Impact factor: 8.171

7.  Escitalopram: superior to citalopram or a chiral chimera?

Authors:  Staffan Svensson; Peter R Mansfield
Journal:  Psychother Psychosom       Date:  2004 Jan-Feb       Impact factor: 17.659

8.  Improved bronchodilation with levalbuterol compared with racemic albuterol in patients with asthma.

Authors:  H S Nelson; G Bensch; W W Pleskow; R DiSantostefano; S DeGraw; D S Reasner; T E Rollins; P D Rubin
Journal:  J Allergy Clin Immunol       Date:  1998-12       Impact factor: 10.793

9.  Efficacy comparison of escitalopram and citalopram in the treatment of major depressive disorder: pooled analysis of placebo-controlled trials.

Authors:  Jack M Gorman; Andrew Korotzer; Guojin Su
Journal:  CNS Spectr       Date:  2002-04       Impact factor: 3.790

10.  Stereoisomers in Psychiatry: The Case of Escitalopram.

Authors:  William J. Burke; Christopher J. Kratochvil
Journal:  Prim Care Companion J Clin Psychiatry       Date:  2002-02
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  9 in total

1.  Pharmaceutical policy regarding generic drugs in Belgium.

Authors:  Steven Simoens; Kristien De Bruyn; Marc Bogaert; Gert Laekeman
Journal:  Pharmacoeconomics       Date:  2005       Impact factor: 4.981

2.  Chiral Switch Drugs for Asthma and Allergies: True Benefit or Marketing Hype.

Authors:  Kathryn Blake; Hengameh Raissy
Journal:  Pediatr Allergy Immunol Pulmonol       Date:  2013-09       Impact factor: 1.349

Review 3.  Optimising acid inhibition treatment.

Authors:  Fernando Gomollón; Xavier Calvet
Journal:  Drugs       Date:  2005       Impact factor: 9.546

Review 4.  Pharmacokinetics of proton pump inhibitors in children.

Authors:  Catherine Litalien; Yves Théorêt; Christophe Faure
Journal:  Clin Pharmacokinet       Date:  2005       Impact factor: 6.447

Review 5.  Insights into the future of gastric acid suppression.

Authors:  Kenneth R DeVault; Nicholas J Talley
Journal:  Nat Rev Gastroenterol Hepatol       Date:  2009-09       Impact factor: 46.802

6.  Gastroparesis associated with gastroesophageal reflux disease and corresponding reflux symptoms may be corrected by radiofrequency ablation of the cardia and esophagogastric junction.

Authors:  Mark D Noar; Emmanuelle Noar
Journal:  Surg Endosc       Date:  2008-04-24       Impact factor: 4.584

7.  Evaluation of Trials Comparing Single-Enantiomer Drugs to Their Racemic Precursors: A Systematic Review.

Authors:  Aaron S Long; Audrey D Zhang; Caitlin E Meyer; Alexander C Egilman; Joseph S Ross; Joshua D Wallach
Journal:  JAMA Netw Open       Date:  2021-05-03

8.  Solid-Phase Conversion of Four Stereoisomers into a Single Enantiomer.

Authors:  Anthonius H J Engwerda; Johannes C J Mertens; Paul Tinnemans; Hugo Meekes; Floris P J T Rutjes; Elias Vlieg
Journal:  Angew Chem Int Ed Engl       Date:  2018-10-19       Impact factor: 15.336

9.  Synthesis and Enantioselective Pharmacokinetic/Pharmacodynamic Analysis of New CNS-Active Sulfamoylphenyl Carbamate Derivatives.

Authors:  Reem Odi; David Bibi; Bella Shusterman; Natalia Erenburg; Chanan Shaul; Claudiu T Supuran; Alessio Nocentini; Meir Bialer
Journal:  Int J Mol Sci       Date:  2021-03-25       Impact factor: 5.923

  9 in total

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