Fluconazole is a triazole broad-spectrum antifungal drug that inhibits Candida tropicalis (IC99=0.20μg/mL) and Candida kefyr (IC99=0.39μg/mL). Fluconazole blocks ergosterol biosynthesis by highly selectively inhibiting fungal cytochrome P450 sterol 14α-demethylase, thereby disrupting the integrity of the fungal cell membrane. Fluconazole can alter cell membrane permeability. Fluconazole can be used in research related to Candida infections and cryptococcal meningitis[1-4].
In vitro, Fluconazole (5-1000μM) was used to treat human adrenocortical carcinoma cell lines (H295R and HAC15) and primary human adrenocortical cell cultures (including normal adrenal glands, ACTH-independent macronodular adrenal hyperplasia, and cortisol-secreting adrenocortical adenomas) for 72 hours. Fluconazole significantly inhibited cortisol production. Fluconazole reduced steroid hormone levels by inhibiting 11β-hydroxylase and 17-hydroxylase activities[5]. Fluconazole (81.6-2612.1μM) was used to treat African green monkey kidney (Vero) cell lines for 24-48 hours, significantly reducing cell viability and inducing necrosis, while increasing micronucleus frequency and DNA damage index[6].
In vivo, Fluconazole (0.1-15mg/kg; oral administration; once daily) was used to treat ICR mice infected with Candida tropicalis for 10 days. Fluconazole significantly improved the survival rate and reduced tissue fungal burden in mice infected with Fluconazole-sensitive strains (510 and 681), but had limited efficacy against Fluconazole-resistant strains (168 and 231)[7]. Fluconazole (2mg/mL; 250μL oral gavage; once daily) was administered to OVA-induced asthmatic C57BL/6 mice for 1 week. Fluconazole significantly worsened lung inflammation and induced lung microbiome dysbiosis[8].
References:
[1] Montero-Gei F. Fluconazole: pharmacokinetics and indications. Arch Med Res. 1993 Winter;24(4):377-85.
[2] Kowalsky SF, Dixon DM. Fluconazole: a new antifungal agent. Clin Pharm. 1991 Mar;10(3):179-94.
[3] Reed BN, Caudle KE, Rogers PD. Fluconazole prophylaxis in high-risk neonates. Ann Pharmacother. 2010 Jan;44(1):178-84.
[4] Silling G. Fluconazole: optimized antifungal therapy based on pharmacokinetics. Mycoses. 2002;45 Suppl 3:39-41.
[5] van der Pas R, Hofland LJ, Hofland J, et al. Fluconazole inhibits human adrenocortical steroidogenesis in vitro. J Endocrinol. 2012 Dec;215(3):403-12.
[6] Correa RMDS, Mota TC, Guimarães AC, et al. Cytotoxic and Genotoxic Effects of Fluconazole on African Green Monkey Kidney (Vero) Cell Line. Biomed Res Int. 2018 Nov 1;2018:6271547.
[7] Graybill JR, Najvar LK, Holmberg JD, et al. Fluconazole, D0870, and flucytosine treatment of disseminated Candida tropicalis infections in mice. Antimicrob Agents Chemother. 1995 Apr;39(4):924-9.
[8] Worasilchai J, Thongchaichayakon P, Chansri K, et al. Fluconazole worsened lung inflammation, partly through lung microbiome dysbiosis in mice with ovalbumin-induced asthma. PeerJ. 2024 Oct 28;12:e18421.