Experimental basis for use of fluconazole for preventive or early treatment of disseminated candidiasis in granulocytopenic hosts

T. J. Walsh, J. Lee, S. Aoki, F. Mechinaud, J. Bacher, J. Lecciones, V. Thomas, M. Rubin, P. A. Pizzo

Research output: Contribution to journalArticle

Abstract

To determine the potential for the use of fluconazole for prevention and treatment of disseminated candidiasis in granulocytopenic patients, we investigated its activity and pharmacokinetics in models of acute, subacute, and chronic forms of disseminated candidiasis in persistently granulocytopenic rabbits. Fluconazole was administered for systemic prophylaxis, early treatment, and delayed treatment. Single-dose and steady-state plasma pharmacokinetics, tissue penetration, and dose-response studies of the investigational compound were studied in subacutely infected granulocytopenic rabbits. Fluconazole was more effective when used for systemic prophylaxis or early treatment of disseminated candidiasis than for delayed treatment. Fluconazole was as effective as amphotericin B plus flucytosine in preventive and early treatment of disseminated candidiasis but was significantly less effective than amphotericin plus flucytosine in the treatment of chronic candidiasis. Dose-response studies demonstrated that the antifungal effect of fluconazole was dose- and time-dependent. Studies of the pharmacokinetics of fluconazole in rabbits demonstrated a long half-life in plasma and a large volume of distribution, properties that correspond to the attainment of high levels of penetration into tissues at multiple organ sites. We conclude that fluconazole is effective for prevention and early treatment of disseminated candidiasis in persistently granulocytopenic rabbits and that the evaluation of its use in preventive or early treatment of disseminated candidiasis is carefully designed clinical trials is warranted.

Original languageEnglish (US)
JournalReviews of Infectious Diseases
Volume12
Issue numberSUPPL. 3
StatePublished - 1990
Externally publishedYes

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Fluconazole
Candidiasis
Rabbits
Flucytosine
Therapeutics
Pharmacokinetics
Amphotericin B
Half-Life
Clinical Trials

ASJC Scopus subject areas

  • Microbiology (medical)

Cite this

Walsh, T. J., Lee, J., Aoki, S., Mechinaud, F., Bacher, J., Lecciones, J., ... Pizzo, P. A. (1990). Experimental basis for use of fluconazole for preventive or early treatment of disseminated candidiasis in granulocytopenic hosts. Reviews of Infectious Diseases, 12(SUPPL. 3).

Experimental basis for use of fluconazole for preventive or early treatment of disseminated candidiasis in granulocytopenic hosts. / Walsh, T. J.; Lee, J.; Aoki, S.; Mechinaud, F.; Bacher, J.; Lecciones, J.; Thomas, V.; Rubin, M.; Pizzo, P. A.

In: Reviews of Infectious Diseases, Vol. 12, No. SUPPL. 3, 1990.

Research output: Contribution to journalArticle

Walsh, TJ, Lee, J, Aoki, S, Mechinaud, F, Bacher, J, Lecciones, J, Thomas, V, Rubin, M & Pizzo, PA 1990, 'Experimental basis for use of fluconazole for preventive or early treatment of disseminated candidiasis in granulocytopenic hosts', Reviews of Infectious Diseases, vol. 12, no. SUPPL. 3.
Walsh, T. J. ; Lee, J. ; Aoki, S. ; Mechinaud, F. ; Bacher, J. ; Lecciones, J. ; Thomas, V. ; Rubin, M. ; Pizzo, P. A. / Experimental basis for use of fluconazole for preventive or early treatment of disseminated candidiasis in granulocytopenic hosts. In: Reviews of Infectious Diseases. 1990 ; Vol. 12, No. SUPPL. 3.
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