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GKV-Arzneimitelindex GKV- Arzneimittelindex Stand: 16. Dezember 2004 Uwe Fricke Anatomisch- Anette Zawinell therapeutisch-chemische Klassifikation mit Tagesdosen für den deutschen Arzneimittel- markt gemäß § 73 Abs. 8 Satz 5 SGB V. – Angenommene Beschlussvorlage der ATC-Arbeitsgruppe des Kuratoriums für Fragen der Klassifikation im Gesundheits- wesen am 3. Dezember 2004 GKV-Arzneimittelindex GKV-Arzneimittelindex Anatomisch-therapeutisch-chemische Klassifikation mit Tagesdosen für den deutschen Arzneimittelmarkt ge- mäß § 73 Abs. 8 Satz 5 SGB V. – Beschlussvorlage für die ATC-Arbeitsgruppe des Kuratoriums für Fragen der Klassifikation im Gesund- heitswesen am 3. Dezember 2004 Bonn, im Dezember 2004 Herausgeber: Wissenschaftliches Institut der AOK (WIdO) Kortrijker Straße 1 53177 Bonn Tel.: 0228/843 393 Fax: 0228/843 144 www.wido.de email: [email protected] Autoren: Prof. Dr. rer. nat. Uwe Fricke Institut für Pharmakologie Klinikum der Universität zu Köln Gleueler Str. 24 50931 Köln email: [email protected] Dr. rer. nat. Anette Zawinell Wissenschaftliches Institut der AOK Kortrijker Str. 1 53177 Bonn email: [email protected] Layout: Heidi Klinger Grafik: Ulrich Birtel Pharmazeutisch-technische Assistenz: Gudrun Billesfeld Sylvia Ehrle Andrea Hall Sandra Heric Manuela Steden Homepage: Aktuelle Informationen zum Thema erhalten Sie unter www.wido.de. 2 GKV-Arzneimittelindex Die vorliegende Publikation wurde im Rahmen des Forschungsprojekts GKV- Arzneimittelindex erstellt: Träger des GKV-Arzneimittelindex AOK-Bundesverband, Bonn BKK Bundesverband, Essen IKK-Bundesverband, Bergisch Gladbach Bundesverband der landwirtschaftlichen Krankenkassen, Kassel Verband der Angestellten-Krankenkassen e.V., Siegburg Arbeiter-Ersatzkassen-Verband e.V., Siegburg Bundesknappschaft, Bochum Kassenärztliche Bundesvereinigung, Berlin Zentralinstitut für die kassenärztliche Versorgung in der Bundesrepublik Deutschland, Berlin ABDA – Bundesvereinigung Deutscher Apothekerverbände/ Deutscher Apo- thekerverband e.V., Berlin Dieses Werk ist urheberrechtlich geschützt. Die dadurch begründeten Rechte, insbesondere die der Übersetzung, des Nachdrucks, des Vortrags, der Ent- nahme von Abbildungen und Tabellen, der Funksendung, der Mikroverfilmung oder der Vervielfältigung auf anderen Wegen und der Speicherung in Daten- verarbeitungsanlagen bleiben auch bei nur auszugsweiser Verwertung vorbe- halten. Eine Vervielfältigung dieses Werkes oder von Teilen dieses Werkes ist auch im Einzelfall nur in den Grenzen der gesetzlichen Bestimmungen des Urheberrechtsgesetzes der Bundesrepublik Deutschland vom 9. September 1965 in der jeweils geltenden Fassung zulässig. Sie ist grundsätzlich vergü- tungspflichtig. Zuwiderhandlungen unterliegen den Strafbestimmungen des Urheberrechtsgesetzes. 3 GKV-Arzneimittelindex Die vorliegende Publikation ist ein Beitrag des GKV-Arzneimittelindex im Wis- senschaftlichen Institut der AOK (WIdO) und weder eine Meinungsäußerung des AOK-Bundesverbandes noch des WHO Collaborating Centre for Drug Statistics Methodology. Die Verwendung von Teilen der Original-WHO- Publikation „Guidelines for ATC classification and DDD assignment“ für die Klassifikationsarbeiten im GKV-Arzneimittelindex im WIdO wurden dem WHO Collaborating Centre for Drug Statistics Methodology angezeigt. Wichtiger Hinweis Die Erkenntnisse in der Medizin unterliegen laufendem Wandel durch For- schung und klinische Erfahrungen. Sie sind darüber hinaus vom wissen- schaftlichen Standpunkt der Beteiligten als Ausdruck wertenden Dafürhaltens geprägt. Wegen der großen Datenfülle sind Unrichtigkeiten gleichwohl nicht immer auszuschließen. Alle Angaben erfolgen insoweit nach bestem Wissen, aber ohne Gewähr. Produkthaftung: Für Angaben über Dosierungshinweise und Applikationsformen können Autoren, Herausgeber und Verlag keine Ge- währ übernehmen. Derartige Angaben müssen vom jeweiligen Anwender im Einzelfall anhand anderer Literaturstellen und anhand der Beipackzettel der verwendeten Präparate in eigener Verantwortung auf ihre Richtigkeit über- prüft werden. 4 GKV-Arzneimittelindex Wissenschaftliche Berater des GKV-Arzneimittelindex: Prof. Dr. med. Björn Lemmer Institut für Pharmakologie und Toxikologie Ruprecht-Karls-Universität Heidelberg Universität Heidelberg Maybachstraße 14-16 68169 Mannheim Prof. Dr. med. Martin J. Lohse Institut für Pharmakologie der Universität Würzburg Versbacher Straße 9 97078 Würzburg Dr. med. Klaus Mengel Höferstr. 15 68199 Mannheim Prof. Dr. med. Gerhard Schmidt Zentrum Pharmakologie und Toxikologie der Universität Göttingen Robert-Koch-Straße 40 37075 Göttingen Prof. Dr. med. Hasso Scholz Institut für Experimentelle und klinische Pharmakologie und Toxikologie Universitäts-Krankenhaus Eppendorf Martinstraße 52 20246 Hamburg 5 Vorwort Vorwort Der GKV-Arzneimittelindex im Wissenschaftlichen Institut der AOK (WIdO) unter der gemeinsamen Trägerschaft der Spitzenverbände der Krankenkas- sen, der Kassenärztlichen Bundesvereinigung, des Zentralinstituts für die kassenärztliche Versorgung sowie der Bundesvereinigung Deutscher Apothe- kerverbände sorgt seit 1981 für Transparenz im deutschen Arzneimittelmarkt. Dabei wird die Erfassung von Umfang und Struktur der vertragsärztlichen Arzneimittelverordnungen in Deutschland erst dadurch ermöglicht, dass das anatomisch-therapeutisch-chemische Klassifikationssystem (ATC-System) der Weltgesundheitsorganisation (WHO) als wesentliche methodische Grund- lage im Rahmen des GKV-Arzneimittelindex verwendet wird. Durch eine Kooperation zwischen der Weltgesundheitsorganisation und dem Wissenschaftlichen Institut der AOK (WIdO) wurde die Anwendung dieses ATC-Klassifikationssystems zur Untersuchung des Arzneimittelverbrauchs auch für den deutschsprachigen Nutzer ermöglicht. Seit Januar 2001 steht damit auch diesem Nutzerkreis das von der Weltgesundheitsorganisation erstellte und gepflegte anatomisch-therapeutisch-chemische Klassifikations- system (ATC-Code) mit definierten Tagesdosen zusammen mit einer ausführ- lichen Methodikbeschreibung in der deutschsprachigen Übersetzung zur Ver- fügung. Im Januar 2004 wurde die international gültige ATC-Klassifikation der WHO durch das Bundesministerium für Gesundheit und Soziale Sicherung (BMGS) für amtlich erklärt. Diese Fassung wurde 2004 über das Deutsche Institut für Medizinische Dokumentation und Information (DIMDI) zur Verfü- gung gestellt. Zur Weiterentwicklung des Klassifikations-Systems mit definierten Tagesdo- sen und einer Anpassung an die besonderen Gegebenheiten des deutschen Arzneimittelmarktes wurde im Auftrag des Bundesministeriums für Gesund- heit und Soziale Sicherung (BMGS) eine Arbeitsgruppe beim Kuratorium für Fragen der Klassifikation im Gesundheitswesen eingesetzt, in der die maß- geblichen Fachkreise vertreten sind. Das Bundesministerium für Gesundheit und Soziale Sicherung (BMGS) hat in Zusammenarbeit mit dieser ATC- Arbeitsgruppe im Jahre 2004 beschlossen, bei der Schaffung einer nationalen ATC/DDD-Klassifikation die bereits vorhandene Adaption der WHO- Klassifikation an den deutschen Markt zu Grunde zu legen, die im Rahmen des langjährigen Forschungsprojekts GKV-Arzneimittelindex (GKV-AI) im Wissenschaftlichen Institut der AOK (WIdO) vorliegt. Mit der nun hier vorlie- genden Stellungnahme des GKV-Arzneimittelindex im WIdO wurden die von den pharmazeutischen Herstellern im Rahmen des Anhörungsverfahrens 6 Vorwort eingesammelten Anmerkungen zur bestehenden ATC-Klassifikation und DDD-Festlegung des GKV-Arzneimittelindex inhaltlich geprüft und entspre- chend bewertet. Der GKV-Arzneimittelindex im WIdO wird die Anpassung der ATC-Klassifikation einschließlich der DDD-Angaben auf Beschluss der ATC- Arbeitsgruppe sowie nach Abstimmung mit dem BMGS vornehmen. Diese Fassung kann dann damit 2005 vom BMGS amtlich gemacht werden. Die große Verbreitung der ATC-Klassifikation und DDD-Systematik – sowohl auf nationaler wie auch auf internationaler Ebene – belegt den hohen prakti- schen Nutzen dieser Klassifikation, die nur durch die engagierte Arbeit von Prof. Dr. Uwe Fricke, Dr. Judith Günther und Dr. Anette Zawinell ermöglicht wird. Für ihre engagierte Arbeit möchten wir uns an dieser Stelle bedanken, da nur ihr unermüdlicher Einsatz eine Klassifikationsdatenbank wie die des GKV-Arzneimittelindex – mit inzwischen mehr als 135.000 Arzneimitteleinträ- gen – am Leben erhält sowie die vorliegende Publikation ermöglicht hat. Wir möchten darüber hinaus den pharmakologischen Gutachtern des GKV- Arzneimittelindex Prof. Dr. Björn Lemmer, Prof. Dr. Martin J. Lohse, Dr. Klaus Mengel, Prof. Dr. Gerhard Schmidt und Prof. Dr. Hasso Scholz unseren be- sonderen Dank für die langjährige fachliche Unterstützung aussprechen. Un- ser Dank gilt weiterhin den pharmazeutischen Assistenzkräften im GKV- Arzneimittelindex Gudrun Billesfeld, Sylvia Ehrle, Andrea Hall, Sandra Heric sowie Manuela Steden für ihre tatkräftige Unterstützung. Darüber hinaus dan- ken wir allen, die bei der Fertigstellung der Stellungnahme mitgewirkt haben. Dabei gebührt der Dank insbesondere Gabi Brückner, Kai Bungarz, Andreas Keller, Heidi Klinger und Ulla Mielke im Wissenschaftlichen Institut der AOK (WIdO), die durch die Datenbetreuung, das Erfassen, die Gestaltung der Tex- te sowie die Durchsicht des Manuskripts zum Gelingen dieses Projekts beige- tragen haben. Bonn, im November 2004 Katrin Nink und Helmut Schröder 7 Inhaltsverzeichnis Inhaltsverzeichnis 1 Einleitung......................................................................................................... 12 1.1 Der GKV-Arzneimittelindex............................................................................................
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  • The Evolving Role of Chemical Synthesis in Antibacterial Drug Discovery Peter M

    The Evolving Role of Chemical Synthesis in Antibacterial Drug Discovery Peter M

    Angewandte. Reviews A. G. Myers et al. DOI: 10.1002/anie.201310843 Antibiotic Development The Evolving Role of Chemical Synthesis in Antibacterial Drug Discovery Peter M. Wright, Ian B. Seiple, and Andrew G. Myers* Keywords: antibiotics · chemical synthesis · drug discovery · semisynthesis Angewandte Chemie &&&& 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim Angew. Chem. Int. Ed. 2014, 53,2–32 Ü Ü These are not the final page numbers! Angewandte Antibacterial Drug Discovery Chemie The discovery and implementation of antibiotics in the early twentieth From the Contents century transformed human health and wellbeing. Chemical synthesis enabled the development of the first antibacterial substances, orga- 1. Introduction 3 noarsenicals and sulfa drugs, but these were soon outshone by a host of 2. Chemical Synthesis Ushers in more powerful and vastly more complex antibiotics from nature: the Golden Age of Antibiotics penicillin, streptomycin, tetracycline, and erythromycin, among others. Discovery 4 These primary defences are now significantly less effective as an unavoidable consequence of rapid evolution of resistance within 3. Semisynthesis: A Powerful Postwar Engine for pathogenic bacteria, made worse by widespread misuse of antibiotics. Antibacterial Discovery 7 For decades medicinal chemists replenished the arsenal of antibiotics by semisynthetic and to a lesser degree fully synthetic routes, but 4. Fully Synthetic Antibacterials, economic factors have led to a subsidence of this effort, which places 1940-Present 13 society on the precipice of a disaster. We believe that the strategic 5. Chemical Synthesis as a Path application of modern chemical synthesis to antibacterial drug Forward 19 discovery must play a critical role if a crisis of global proportions is to be averted.
  • 23S Rrna Base Pair 2057–2611 Determines Ketolide Susceptibility and Fitness Cost of the Macrolide Resistance Mutation 2058A3G

    23S Rrna Base Pair 2057–2611 Determines Ketolide Susceptibility and Fitness Cost of the Macrolide Resistance Mutation 2058A3G

    23S rRNA base pair 2057–2611 determines ketolide susceptibility and fitness cost of the macrolide resistance mutation 2058A3G Peter Pfister*†, Natascia Corti*†, Sven Hobbie*, Christian Bruell*, Raz Zarivach‡, Ada Yonath‡§, and Erik C. Bo¨ ttger*§ *Institut fu¨r Medizinische Mikrobiologie, Universita¨t Zu¨ rich, Gloriastrasse 30͞32, CH-8006 Zu¨rich, Switzerland; and ‡Department of Structural Biology, Weizmann Institute, Rehovot 76100, Israel Contributed by Ada Yonath, February 27, 2005 The 23S rRNA A2058G alteration mediates macrolide, lincosamide, Mycobacterium intracellulare (14), Mycobacterium avium (15, 16), and streptogramin B resistance in the bacterial domain and deter- Mycobacterium kansasii (17), Mycobacterium chelonae, Mycobacte- mines the selectivity of macrolide antibiotics for eubacterial ribo- rium abscessus (18), Helicobacter pylori (19–21), Brachyspira (Ser- somes, as opposed to eukaryotic ribosomes. However, this muta- pulina) hyodysenteriae (22), Propionibacterium spp. (23), and Strep- tion is associated with a disparate resistance phenotype: It confers tococcus pneumoniae (24). These mutations have been mapped to high-level resistance to ketolides in mycobacteria but only mar- the macrolide-binding pocket in the ribosomal tunnel, specifically ginally affects ketolide susceptibility in streptococci. We used 23S rRNA nucleotides 2057, 2058, and 2059 in the Escherichia coli site-directed mutagenesis of nucleotides within domain V of 23S numbering system. rRNA to study the molecular basis for this disparity. We show that Nucleotides 2058 and 2059 act as key contact sites for macrolide mutational alteration of the polymorphic 2057–2611 base pair from binding (2, 25). Site-directed mutagenesis has been used to analyze A-U to G-C in isogenic mutants of Mycobacterium smegmatis in detail the role of 23S rRNA nucleotides 2058 and 2059 in significantly affects susceptibility to ketolides but does not influ- drug-target interaction; these studies also alluded to the importance ence susceptibility to other macrolide antibiotics.