New methods of delivery of amphotericin B.
Fungal infections continue to be a major problem in the management of immunocompromised patients. Despite its formidable toxicity and treatment failures, amphotericin B is still the drug of choice for most of these infections. One strategy for reducing the toxicity of amphotericin B and thus permitting administration of higher doses is that of using less toxic formulations. Entrapping amphotericin B into liposomes or binding it to other substances reduces its toxicity to host cells, whereas the selective binding of amphotericin B to ergosterol preserves its toxicity to fungal cells. Adding fungus-specific antibodies to such liposomes may further increase the efficiency of drug targeting. The initial unpublished data from controlled clinical trials of various liposomal preparations of amphotericin B are less encouraging than anticipated, but additional trials are needed for a proper evaluation. Another strategy for improving efficacy of amphotericin B is that of bringing it directly into contact with the body sites most likely to be infected. Intranasal delivery of amphotericin B for prevention of invasive aspergillosis has been evaluated in at least three different clinical trials with conflicting results; no controlled trials are available. Prophylactic administration of low doses of amphotericin B as an aerosol was the most effective of the regimens tested in an animal model of pulmonary aspergillosis and was also judged to be effective in a clinical trial using historical controls. Independent of the route of administration, in both an animal model was various clinical studies, early administration of amphotericin B was more effective than late administration.(ABSTRACT TRUNCATED AT 250 WORDS)
Schmitt
H J
HJ
Children's Hospital, Johannes Gutenberg University, Mainz, Germany.
D000281:Administration, Intranasal; D000336:Aerosols; D000666:Amphotericin B / Q000008:administration & dosage*; D000818:Animals; D001228:Aspergillosis / Q000188:drug therapy; D004304:Dosage Forms; D006801:Humans; D016867:Immunocompromised Host; D009181:Mycoses / Q000188:drug therapy*; D013997:Time Factors
D000336:Aerosols; D004304:Dosage Forms; D000666:Amphotericin B