Abstract
Fluconazole is a novel triazole antifungal drug chiefly used in the treatment of opportunistic mycoses in immuno-compromised patients, particularly those with the acquired immuno-deficiency syndrome (AIDS). In comparison with other antifungal drugs, fluconazole has outstanding physical and pharmacokinetic properties, such as an excellent aqueous solubility allowing a parenteral formulation, high bioavailability by the oral route, even distribution throughout the tissues, including the central nervous system and the cerebro-spinal fluid, a long half-life (permitting once daily administration), and low binding to plasma proteins. It is excreted mainly as unchanged drug in the urine. Fluconazole is a broad-spectrum antifungal agent, especially effective againstCandida spp.,Cryptococcus neoformans and dermatophytes. Its antifungal efficacy was mainly proved by testing in animal models, since there is no relationship betweenin vitro andin vivo activities. It possesses a low toxicity and it is well-tolerated. Fluconazole is currently marketed for the treatment of oropharyngeal candidiasis in immuno-compromised patients and of atrophic oral candidiasis. Its place in the treatment of opportunistic mycoses in human immuno-deficiency virus-positive patients, in particular cryptococcal meningitis, is still under investigation but is promising.
Similar content being viewed by others
References
Marriott MS, Richardson K. The discovery and mode of action of fluconazole. In: Promtling RA, ed. Recent trends in the discovery, development and evaluation of antifungal agents. Barcelona: J.R. Prous Science Publishers, 1987:81–92.
Perfect JR, Durack DT. Penetration of imidazoles and triazoles into cerebrospinal fluid of rabbits. J Antimicrob Chemother 1985;16:81–6.
Shaw JT, Tarbit MH, Troke PF. Cytochrome P-450 mediated sterol synthesis and metabolism: differences in sensitivity of fluconazole and other azoles. In: Fromtling RA, ed. Recent trends in the discovery, development and evaluation of antifungal agents. Barcelona: J.R. Prous Science Publishers, 1987:125–40.
Houston JB, Humphrey MJ, Matthew DE, Tarbit MH. Comparison of two antifungal drugs, ketoconazole and fluconazole, as modifiers of rat hepatic monooxygenase activity. Biochem Pharmacol 1988;37:401–8.
Hanger DP, Jevons S, Shaw JTB. Fluconazole and testosterone:in vivo andin vitro studies. Antimicrob Agents Chemother 1988;32:646–8.
Odds FC, Cheesman SL, Abbott AB. Antifungal effects of fluconazole, a new triazole antifungal,in vitro. J Antimicrob Chemother 1986;18:473–8.
Galgiani JN. Fluconazole, a new antifungal agent. Ann Intern Med 1990;113:177–9.
Galgiani JN. Susceptibility ofCandida albicans and other yeasts to fluconazole: relation betweenin vitro andin vivo studies. Rev Infect Dis 1990;12:S272–5.
Gordon MA, Lapa EW, Passero PA. Improved method for azole antifungal susceptibility testing. J Clin Microb 1988;26:1874–7.
Troke PF, Andrews RJ, Brammer KW, Marriott MS, Richardson K. Efficacy of UK-49, 858 (fluconazole) againstCandida albicans experimental infections in mice. Antimicrob Agents Chemother 1985;28:815–8.
Troke PF. Efficacy of fluconazole in animal models of superficial and opportunistic systemic fungal infection. In: Fromtling RA, ed. Recent trends in the discovery, development and evaluation of antifungal agents. Barcelona: J.R. Prous Science Publishers, 1987:103–12.
Richardson K, Andrews RJ, Marriott MS, Troke PF. UK-49,858.In vivo activity of a potent oral agent against systemic fungal infections. In: Ishigami J, ed. Recent advances in chemotherapy. Proceedings of the 14th International Congress of Chemotherapy. Tokyo: University of Tokyo Press, 1985:1940–1.
Van 't Wout JW, Mattie H, Van Furth R. Comparison of the efficacies of Amphotericin B, fluconazole, and itraconazole against a systemicCandida albicans infection in normal and neutropenic mice. Antimicrob Agents Chemother 1989;33:147–51.
Hughes CE, Bennett RL, Tuna IC, Beggs WH. Activities of fluconazole (UK 49,858) and ketonazole against ketonazole susceptible and resistantCandida albicans. Antimicrob Agents Chemother 1988;32:209–12.
Palou De Fernandez E, Patino MM, Graybill JR, Tarbit MH. Treatment of experimental cryptococcal meningitis with an antifungal triazole, fluconazole (UK-49,858). J Antimicrob Chemother 1986;18:261–70.
Troke PF, Andrews RJ, Marriott MS, Richardson K. Efficacy of fluconazole against experimental aspergillosis and cryptococcosis in mice. J Antimicrob Chemother 1987;19:663–70.
Perfect JR, Savani DV, Durack DT. Comparison of itraconzole and fluconazole in treatment of cryptococcal meningitis and Candida pyelonephritis in rabbits. Antimicrob Agents Chemother 1986;29:579–83.
Graybill JR. Fluconazole efficacy in animal models of mycotic diseases. In: Fromtling RA, ed. Recent trends in the discovery, development and evaluation of antifungal agents. Barcelona: J.R. Prous Science Publishers, 1987:113–24.
Graybill JR, Palou E, Ahrens J. Treatment of murine histoplasmosis with UK 49,858 (fluconazole). Am Rev Resp Dis 1986;134:768–70.
Kobayashi GS, Travis S, Medoff G. Comparison of thein vitro andin vivo activity of the bis triazole derivative UK 49,858 with that of amphotericin B againstHistoplasma capsulatum. Antimicrob Agents Chemother 1986;29:660–2.
Pappagianis D, Crane R. Survival in coccidioida meningitis since introduction of amphotericin B. In: Ajello L, ed. Coccidioidomycosis: current clinical and diagnosis status. Miami: Symposia Specialists, 1977:239–51.
Lyman CA, Sugar AM, Diamond RD. Comparative activities of UK-49,858 and amphotericin B againstBlastomyces dermatitidis infections in mice. Antimicrob Agents Chemother 1986;29:161–2.
Richardson K, Brammer KW, Marriott MS, Troke PF. Activity of UK-49,858, a bis-triazole derivative against experimental infections withCandida albicans andTrichophyton mentagrophytes. Antimicrob Agents Chemother 1985;27:832–5.
Marriot MS, Andrews RJ, Richardson K, Troke PF. The antifungal activity of UK-49,858 in animal models of superficial infections. In: Ishigami J, ed. Recent advances in chemotherapy. Proceedings of the 14th international congress of chemotherapy. Tokyo: University of Tokyo Press, 1985:1936–7.
De Wit S, Clumeck N. Fluconazole in the treatment of fungal infections associated with AIDS. Infection 1989;17:121–3.
Walsh TJ, Pizzo A. Treatment of systemic fungal infections: recent progress and current problems. Eur J Clin Microbiol Infect Dis 1988;7:460–75.
Brammer KW, Farrow PR, Faulkner JK. Pharmaco-kinetics and tissue penetration of fluconazole in humans. Rev Infect Dis 1990;12:S318–26.
Brammer KW, Tarbit MH. A review of the pharmacokinetics of fluconazole (UK-49,858) in laboratory animals and man. In: Fromtling RA, ed. Recent trends in the discovery, development and evaluation of antifungal agents. Barcelona: J.R. Prous Science Publishers, 1987:141–9.
Humphrey MJ, Jevons S, Tarbit MH. Pharmacokinetic evaluation of UK-49,858, a metabolitically stable triazole antifungal drug, in animals and humans. Antimicrob Agents Chemother 1985;28:648–53.
Foulds G, Wajszczuk C, Weidler DJ, Garg DC, Gibson P. Steady state parenteral kinetics of fluconazole in man. Abstract of the first international conference on drug research in immunologic and infection disease. Antifungal drugs: synthesis, preclinical and clinical evaluation. New York, 1987.
Walsh TJ, Fould G, Pizzo PH. Pharmacokinetics and tissue penetration of fluconazole in rabbits. Antimicrob Agents Chemother 1989;33:467–9.
Arndt CA, Walsh TJ, McCully CL, Bails FM, Pizzo PA, Poplack DG. Fluconazole penetration into cerebrospinal fluid: implications for treating fungal infections of the central nervous system. J Infect Dis 1988;157:178–80.
Foulds G, Brennan DR, Wajszczuk C, et al. Fluconazole penetration into cerebrospinal fluid in humans. J Clin Pharmacol 1988;28:363–6.
Tucker RM, Williams PL, Arathoon EG, et al. Pharmacokinetics of fluconazole in cerebrospinal fluid and serum in human coccidioidal meningitis. Antimicrob Agents Chemother 1988;32:369–73.
Classen DC, Burke JP, Smith CB. Treatment of coccidioidal meningitis with fluconazole. J Infect Dis 1988;158:903–4.
Stern JJ, Hartman BJ, Sharkey P, et al. Oral fluconazole therapy for patients with acquired immunodeficiency syndrome and cryptococcosis: experience with 22 patients. Am J Med 1988;85:477–80.
Savani DV, Perfect JR, Cobo LM, Durack DT. Penetration of new azole compounds into the eye and efficacy in experimentalCandida endophtalmitis. Antimicrob Agents Chemother 1987;31:6–10.
Schulman JA, Peyman G, Coats M. Toxicity of intravitreal fluconazole in rabbits: an extended abstract. Rev Infect Dis 1990;12:S303.
Anonymous. Report of international multicentre trial: a comparison of single-dose oral fluconazole with 3 days intra-vaginal clotrimazole in treatment of vaginal candidiasis. Br J Obstet Gynaecol 1989;96:226–32.
Lassus A, Virrankoski T, Eskelinen A, Kappa E. An open study to compare efficacy, safety and toleration of a single oral dose of fluconazole (UK-49,858) and clotrimazole intravaginal tablets given once daily for 3 days in the treatment of patients with vaginal candidosis. Abstract of the second world congress on sexually transmitted diseases. Paris, June 1986.
Brammer KW. Treatment of vaginal candidiasis with a single oral dose of fluconazole. Eur J Clin Microbiol Infect Dis 1988;7:364–7.
Kutzer E, Oittner R, Leodolter S, Brammer KW. A comparison of fluconazole and ketoconazole in the oral treatment of vaginal candidiasis; report of a double-blind multicentre trial. Eur J Obstet Gynecol Reprod Biol 1988;29:305–13.
Naeyaert JM, De Bersaques J, De Cuyper C, Hindryckx P, Van Landuyt H, Gordts B. Fluconazole (UK-49,858): a novel oral antifungal in the treatment of fungal skin infections. Results of an open study in 43 patients. In: Fromtling RA, ed. Recent trends in the discovery, development and evaluation of antifungal agents. Barcelona: J.R. Prous Science Publishers, 1987:157–61.
Saag MS, Dismukes WE. Azole antifungal agents: emphasis on new triazoles. Antimicrob Agents Chemother 1988;32:1–8.
De Witts S, Weerts D, Goossens H, Clumeck N. Comparison of fluconazole and ketonazole for oropharyngeal candidiasis in AIDS. Lancet 1989;1:746–7.
Kirk AJB, Gould FK, Freeman R, Corris PA, Dark JH. Fluconazole and candidiasis. Lancet 1989;1:339.
Larsen RA, Leal MAE, Chan LS. Fluconazole compared with amphotericin B plus flucytosine for cryptococcal meningitis in AIDS. A randomized trial. Ann Intern Med 1990;113:183–7.
Van't Wout JW, Mattie H, Van Furth R. A prospective study of the efficacy of fluconazole (UK-49,858) against deep-seated fungal infections. J Antimicrob Chemother 1988;21:665–72.
Kujath P, Lerch K. Secondary mycosis in surgery: treatment with fluconazole. Infection 1989;17:111–7.
Dupont B, Drouhet E. Fluconazole in the management of oropharyngeal candidosis in a predominantly HIV antibody-positive group of patients. J Med Vet Mycol 1988;26:67–71.
Meunier F, Gerain J, Snoeck R, Libotte F, Lambert C, Ceuppens AM. Fluconazole therapy of oropharyngeal candidiasis in cancer patients. In: Fromtling RA, ed. Recent trends in the discovery, development and evaluation of antifungal agents. Barcelona: J.R. Prous Science Publishers, 1987:169–74.
Chane JP, Cajot A, Bille J, Glauser MP. Single-dose therapy for oral candidiasis with fluconazole in HIV infected adults: a pilot study. J Infect Dis 1989;159:806–7.
Leen CS, Dunbar EM, Ellis ME, Mandal BK. Once weekly fluconazole to prevent recurrence of oropharyngeal candidiasis in patients with AIDS and AIDS related complex: a double blind placebo controlled study. J Infect 1990;21:55–60.
Cohen J. Treatment of systemic yeast infection with fluconazole. J Antimicrob Chemother 1989;23:294–5.
Dave J, Hickey MM, Wilkins EGL. Fluconazole in renal candidiasis. Lancet 1989;1:163–4.
Isalska BJ, Stanbridge TN. Fluconazole in the treatment of candidal prosthetic valve endocarditis. Br Med J 1988;297:178–9.
Warnock DW, Burke J, Cope NJ, Johnson EM, Von Fraunhofer NA, Williams EW. Fluconazole resistant inCandida glabrata. Lancet 1988;2:1310.
Eng RH, Bishburg E, Smith SM, Kapila R. Cryptococcal infections in patients with AIDS. Am J Med 1986;81:19–23.
Dismukes WE. Cryptococcal meningitis in patients with AIDS. J Infect Dis 1988;157:624–8.
Zuger A, Louie E, Holzman RS, Simberkoff MSS, Rahal JJ. Cryptococcal disease in patients with AIDS. Ann Intern Med 1986;104:234–40.
Dupont B, Drouhet E. Cryptocococcal meningitis and fluconazole. Ann Intern Med 1987;106:778.
Dupont B, Drouhet E. Fluconazole for the treatment of fungal diseases in immunosuppressed patients. First international conference on drug research in immunologic and infectious diseases: antifungal drugs. Synthesis, pre-clinical and clinical evaluation [Abstract]. NY Acad Sci 1987.
Dupont B. Treatment of cryptococcal meningitis. In: Torres-Rodriguez JM, ed. Proceedings of the 10th congress of the International Society for Human and Animal Mycology (ISHAM), June 27–July 1, 1988, Barcelona. Barcelona: J.R. Prous Science Publishers, 1988:197–8.
Byrne WR, Wajszczuck CP. Cryptococcal meningitis in the AIDS: successful treatment with fluconazole after failure of amphotericin B. Ann Intern Med 1988;108:384–5.
Van 't Wout JW, De Graeff-Meeder ER, Paul LC, Kuis W, Van Furth R. Treatment of the cases of cryptococcal meningitis with fluconazole. Scand J Infect Dis 1988;20:193–8.
Esposito R, Uberti Foppa C, Antinori S. Fluconazole for cryptococcal meningitis.
Franklin IM, Elias E, Hirsch C. Fluconazole-induced jaundice. Lancet 1990;2:565.
Kidd D, Ranaghan EA, Morris TCM. Hypokalaemia in patients with acute myeloid leukaemia after treatment with fluconazole. Lancet 1989;1:1017.
Suger A, Saunders C, Idelson BA, Bernard DB. Interaction of fluconazole and cyclosporine. Ann Intern Med 1989;110:844.
Collignon P, Hurley B, Mitchell D. Interaction of fluconazole with cyclosporin. Lancet 1989;1:1262.
Ehninger G, Jaschonek K, Shuer U, Kruger HU. Interaction of fluconazole with cyclosporin. Lancet 1989;2:104–5.
Mitchell AS, Holland JT. Fluconazole and phenytoin: a predictable interaction. Br Med J 1989;298:1315.
Lazar JD, Wilner KD. Drug interactions with fluconazole. Rev Infect Dis 1990;12:S327–33.
Terrel CHL, Hermans PE. Antifungal agents used for deep-seated mycotic infections. Mayo Clin Proc 1987;62:116–28.
Polski B, Depman M, Gold JWM, Galicich JH, Amstrong D. Intraventricular therapy of cryptococcal meningitis via a subcutaneous reservoir. Am J Med 1985;81:24–8.
Bennett JE, Dismukes WE, Duma RJ, et al. A comparison of amphotericin B alone and combined with flucytosine in the treatment of cryptococcal meningitis. N Engl J Med 1979;301:126–31.
Denning DW, Tucker RM, Hanson LH, Hamilton JR, Stevens DA. Intraconazole therapy for cryptococcal meningitis and cryptococcosis. Arch Intern Med 1989;149:2301–8.
Einsele H, Jaschonek K, Steinhilber D, Ehninger G, Roth HJ. Fluconazole versus Ketonazole in oropharyngeal candidiasis in AIDS. Lancet 1989;1:1130.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Vincent-Ballereau, F.N., Patey, O.N. & Lafaix, C. Fluconazole. Pharmaceutisch Weekblad Scientific Edition 13, 45–57 (1991). https://doi.org/10.1007/BF01974981
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01974981