Document 0761
 DOCN  M9460761
 TI    Cryptococcal meningitis: the place of itraconazole.
 DT    9404
 AU    Cauwenbergh G; Department of Clinical Research and Development, Janssen
       Research; Foundation, Beerse, Belgium.
 SO    Mycoses. 1993 Jul-Aug;36(7-8):221-8. Unique Identifier : AIDSLINE
       MED/94158948
 AB    Itraconazole, an orally active broad-spectrum triazole antimycotic, has
       demonstrated anti-Cryptococcus activity in vitro and in animal models of
       cryptococcal meningitis. The drug has been used by a number of clinical
       groups for the treatment of cryptococcal meningitis, predominantly in
       AIDS patients. A problem that has been found with ketoconazole is the
       relatively low absorption of the drug in AIDS patients. This has
       resulted in ketoconazole plasma levels below the MIC90 (1-5 micrograms
       ml-1) needed to eliminate Cryptococcus neoformans. In addition, tissue
       levels of ketoconazole are lower than plasma levels. For itraconazole,
       the required MIC90 for Cr. neoformans is 0.1 microgram ml-1, and the
       plasma levels in AIDS patients receiving 200-400 mg daily, even in the
       case of reduced absorption, are well above this MIC90. The itraconazole
       levels in the brain and in the meninges are higher than the plasma
       levels. Consequently, itraconazole has been considered a valid candidate
       for studies in patients with cryptococcal meningitis. Various treatment
       modalities have been used: primary oral therapy alone or in combination
       with amphotericin B or 5-fluorocytosine (5-FC); maintenance oral therapy
       after initial treatment with amphotericin B (with or without 5-FC); and
       first-line intravenous treatment in severely ill patients. The results
       were evaluated in four different groups. When the drug was given as
       primary oral therapy without combination with amphotericin B or 5-FC,
       the results depended greatly on the dose administered and on the life
       expectancy of the patient at inclusion. In general, daily doses of 400
       mg were better than 200-mg doses.(ABSTRACT TRUNCATED AT 250 WORDS)
 DE    AIDS-Related Opportunistic Infections/*DRUG THERAPY  Cryptococcus
       neoformans/DRUG EFFECTS  Human  Itraconazole/PHARMACOLOGY/*THERAPEUTIC
       USE  Meningitis, Cryptococcal/COMPLICATIONS/*DRUG THERAPY  JOURNAL
       ARTICLE  REVIEW  REVIEW, TUTORIAL

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