Abstract
Invasive mycoses are important causes for treatment related morbidity and mortality
in severely immunocompromised pediatric patients with hematological malignancies or
hematopoietic stem cell transplantation. The past decade has witnessed a major expansion
of antifungal drug research, which has resulted in the development of the novel class
of echinocandin lipopeptides (anidulafungin, micafungin, caspofungin) and a new generation
of antifungal triazoles with improved pharmacological properties (posaconazole, ravuconazole,
voriconazole). Whereas caspofungin and voriconazole have been licensed in the European
Union, the United States, Canada and several other countries throughout the world,
posaconazole, ravuconazole, anidulafungin and micafungin are under regulatory review
or in advanced stages of clinical development. Caspofungin and voriconazole are increasingly
prescribed in pediatric patients, although pediatric dosage finding and safety evaluations
have not been completed. This article reviews the clinical pharmacology of the new
antifungal agents and the status of their clinical development in immunocompromised
pediatric patients.
Zusammenfassung
Invasive Pilzinfektionen sind wichtige Ursachen von Morbidität und Mortalität bei
der Behandlung abwehrgeschwächter Kinder und Jugendlicher mit hämatologischen Neoplasien
oder hämatopoetischer Stammzell-Transplantation. Das vergangene Jahrzehnt hat eine
intensivierte Forschung auf dem Gebiet der antimykotischen Chemotherapie erlebt, die
zu der Entwicklung der neuen Substanzklasse der Echinocandine (Anidulafungin, Micafungin,
Caspofungin) und einer neuen Generation von antimykotischen Triazolen mit verbesserten
pharmakologischen Eigenschaften (Posaconazol, Ravuconazol, Voriconazol) geführt hat.
Während Caspofungin und Voriconazol in der Europäischen Union, den Vereinigten Staaten,
Kanada und mehreren anderen Ländern zugelassen ist, befinden sich Posaconazol, Ravuconazol,
Anidulafungin und Micafungin in Evaluation durch die Zulassungsbehörden bzw. in fortgeschrittenen
Stadien der klinischen Entwicklung. Caspofungin und Voriconazole werden zunehmend
bei pädiatrische Patienten eingesetzt, obwohl Dosisfindung und Prüfung von Sicherheit
und Verträglichkeit in dieser Population nicht abgeschlossen sind. Die vorliegende
Arbeit gibt eine Übersicht über die klinische Pharmakologie der neuen antimykotischen
Substanzen und über den derzeitigen Stand ihrer klinischen Entwicklung bei abwehrgeschwächten
Kindern und Jugendlichen.
Key words
antifungal agents - voriconazole - caspofungin - mycoses - cancer - children
Schlüsselwörter
Antimykotika - Voriconazol - Caspofungin - Pilzinfektionen - Krebs - Kinder
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Andreas H. GrollM. D.
Infectious Disease Research Program · Department of Pediatric Hematology and Oncology
· University Children's Hospital
Albert-Schweitzer-Strasse 33
48129 Muenster
Germany
Phone: +49/2 51/8 35 28 01
Fax: +49/2 51/8 35 28 04
Email: grollan@mednet.uni-muenster.de
