Zusammenfassung
Etwa 25 % der gebräuchlichen Medikamente liegen als Racemate vor, also als Mischung
ihrer optischen oder räumlichen (Stereo-)Isomere (Enantiomere). Häufig unterscheiden
sich die Enantiomere hinsichtlich Pharmakokinetik, Pharmakodynamik und Nebenwirkungsprofil.
Die Entwicklung von Enantiomeren als Medikament stößt daher auf zunehmendes Interesse
von Industrie, Pharmakologen und Klinikern. Seitdem die technologischen Voraussetzungen
für Darstellung und Stabilisierung von Enantiomeren in den letzten 10 Jahren geschaffen
wurden, schenken auch die Zulassungsbehörden der Chiralität („Händigkeit”) von Medikamenten
ihre Aufmerksamkeit, indem sie eine „chirale Umschaltung” („chiral switch”) empfehlen
und fördern. Typische, von der Chiralität abhängige Probleme von Medikamenten werden
referiert. Abschließend wird der therapeutische Gewinn aufgezeigt, der durch eine
chirale Umschaltung von Omeprazol auf sein Enantiomer (S)-Omeprazol („Esomeprazol”)
erreicht wurde. Mit Esomeprazol wurde der erste isomere Protonenpumpeninhibitor (iPPI)
entwickelt und zur Therapie säureinduzierter Krankheiten eingeführt.
Chiral switch, a successful way to drug development: Example esomeprazole
About 25 % of common drugs are racemates, i. e. mixtures of their optical or spatial
isomers (stereoisomers or enantiomers). Frequently the enantiomers differ in their
pharmacokinetics, pharmacodynamics, drug interactions and side effects. Therefore,
the pharmaceutical industry, pharmacologists and clinicians are increasingly interested
in the development of enantiomers as drugs. Since advances in synthetic and analytical
chemistry have provided the tools to produce stereoisomeric drugs, also the authorities
recommend and support chiral switch. As example for the therapeutic gain the recent
studies with esomeprazole, the first isomeric protonpump inhibitor (iPPI) are summarized
and discussed.
Schlüsselwörter
Chiralität - chirale Umschaltung - Enantiomer - isomerer Protonenpumpeninhibitor -
Esomeprazol -
Key words
Chirality - Chiral Switch - Enantiomer - Isomeric Protonpump Inhibitor - Esomeprazole
-
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Anschrift des Verfassers
Prof. Dr. med. Werner Creutzfeldt
Zentrum Innere Medizin Georg-August Universität
Robert-Koch-Straße 40
37075 Göttingen
