Fluconazole

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.

Fluconazole是一种三唑类广谱抗真菌药物，可抑制C. albicans（IC₉₉=0.20μg/mL）和Candida kefyr（IC₉₉=0.39μg/mL）。Fluconazole可通过高度选择性抑制真菌细胞色素P450甾醇14α-去甲基化酶来阻断麦角甾醇的生物合成，从而破坏真菌细胞膜的完整性。Fluconazole还可改变细胞膜的通透性。Fluconazole可用于念珠菌感染和隐球菌脑膜炎的相关研究^[1-4]。

在体外，Fluconazole（5-1000μM）处理人类肾上腺皮质癌细胞系（H295R和HAC15）及人类肾上腺皮质原代培养细胞（包括正常肾上腺、ACTH非依赖性大结节性肾上腺增生和皮质醇分泌性肾上腺皮质腺瘤）72h。Fluconazole显著抑制皮质醇的产生。Fluconazole通过抑制11β-羟化酶和17-羟化酶活性降低类固醇激素水平^[5]。Fluconazole（81.6-2612.1μM）处理非洲绿猴肾(Vero)细胞系24-48小时，显著降低细胞存活率并诱导坏死，同时增加微核频率和DNA损伤指数^[6]。

在体内，Fluconazole（0.1-15mg/kg；口服；每日一次）处理感染C. albicans的ICR小鼠，连续10天，显著提高了对氟康唑敏感菌株（510和681）感染小鼠的生存率并降低了组织载菌量，但对氟康唑耐药菌株（168和231）效果有限^[7]。Fluconazole（2mg/mL；口服250μL；每日一次）用于处理OVA诱导的哮喘C57BL/6小鼠，持续1周。Fluconazole显著加重了肺炎症，并引起肺微生物组失调^[8]。