Summary
Amphotericin B is the only antifungal drug which, despite its dose-limiting toxicity, can be given intravenously when an aggressive treatment is required. In an attempt to reduce the drug toxicity while retaining its therapeutic efficacy, new formulations of amphotericin B have been developed. The most promising have employed lipid vehicles such as liposomes. Three lipid-based amphotericin B formulations have been developed by pharmaceutical companies and are under active clinical investigation. Efficacy and safety data of these derivatives in animals and humans are reviewed, with particular concern to cryptococcal infection. The authors' experience with a small unilamellar liposomal amphotericin B formulation, AmBisome, in the primary therapy of cryptococcosis is reported. Nine AIDS patients affected with cryptococcosis, seven of whom had meningitis, were given AmBisome (3 mg/kg/day) for 3–6 weeks. Complete response was obtained in six patients, marked improvement in two, and failure in one. AmBisome was well tolerated and shortened the time to clinical and mycological response suggesting a further improvement in the management of cryptococcosis in AIDS patients.
Zusammenfassung
Amphotericin B ist die einzige antimykotisch wirkende Substanz, die trotz ihrer dosislimitierenden Toxizität intravenös gegeben werden kann, wenn eine aggressive Behandlung erforderlich ist. In der Absicht, die medikamentös-toxischen Nebenwirkungen bei gleichbleibender therapeutischer Wirksamkeit zu reduzieren, wurden neue Formulierungen von Amphotericin B entwickelt. Am erfolgversprechendsten erwies sich bisher die Verwendung von Lipiden als Trägersubstanzen. Bis jetzt wurden drei lipid-gebundene Amphotericin-B-Formulierungen von pharmazeutischen Unternehemen entwickelt, die zur Zeit klinisch geprüft werden. Es werden Angaben zur Wirksamkeit und Verträglichkeit dieser Derivate bei Tieren und Menschen zusammenfassend dargestellt, insbesondere unter Berücksichtigung der Kryptokokken-Infektion. Die Autoren berichten über ihre Erfahrungen mit einer kleinen unilamellären liposomalen Amphotericin-B-Formulierung (AmBisome™) in der Primärtherapie der Kryptokokkose. Neun Patienten mit AIDS und Kryptokokken-Infektion (sieben Patienten hiervon mit Meningitis) erhielten AmBisome™ (3 mg/kg/Tag) über 3–6 Wochen. Vollständige Remissionen wurden bei sechs Patienten erreicht, eine deutliche Besserung bei zwei Patienten. Bei einem Patienten versagte die Therapie. AmBisome™ wurde gut vertragen und verkürzte das Zeitintervall bis zur klinischen und mykologischen Besserung, was eine weitere Verbesserung in der Therapie der Kryptokokkose bedeuten kann.
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Viviani, M.A., Tortorano, A.M., Roverselli, A.M. et al. Lipid-based amphotericin B in the treatment of cryptococcosis. Infection 22, 137–142 (1994). https://doi.org/10.1007/BF01739025
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DOI: https://doi.org/10.1007/BF01739025