Shahid Sadoughi University of Medical Sciences https://en.ssu.ac.ir/publications/ Advances in Pharmacology and Therapeutics Journal 2783-3445 5 1 2025 03 16 In Vitro Antifungal Effects of Duloxetine in Combination with Fluconazole on Fluconazole-Resistant Candida Albicans 20 30 417 10.18502/aptj.v5i1.18132 EN Ehsan Momeni Abbas Alimoradian Mojtaba Didehdar Ali Tajic Malihe Safari Journal Article 2025 01 18 Aim: This study evaluate the antifungal effects of duloxetine as monotherapy and in combination with fluconazole on fluconazole-resistant C. albicans. Methods: In this in vitro study, a suspension of fluconazole-resistant C. albicans clinical isolates from oral candidiasis was prepared using the CLSI M37-A3 method. Fluconazole (3 mg/mL) and duloxetine (160 µg/mL) stock solutions were serially diluted 9 times (0.625-160 µg/mL for duloxetine and 0.5-128 µg/mL for fluconazole). Their antifungal activity against C. albicans were evaluated by the microdilution method through broth media. The minimum inhibitory concentration of duloxetine, fluconazole, and their combination was also determined. Results: Fluconazole-resistant C. albicans was only sensitive to 32, 64, and 128 µg/mL fluconazole and 160, 80, and 40 µg/mL duloxetine as monotherapy. It was also sensitive to 80 and 160 µg/mL duloxetine combined with all 9 dilutions of fluconazole, but 40 µg/mL duloxetine was only effective in combination with 16 to 128 µg/mL fluconazole. Fluconazole-resistant C. albicans was sensitive to 10 and 20 µg/mL duloxetine combined with 32, 64, and 128 µg/mL fluconazole. It was also sensitive to 0.625, 1.25, 2.5, and 5 µg/mL duloxetine combined with 64 and 128 µg/mL fluconazole. The MIC of duloxetine was 40 µg/mL as monotherapy and 16 µg/mL combined with fluconazole. Conclusion: Duloxetine had antifungal effects and the combination of duloxetine with fluconazole had synergistic effects on inhibited fluconazole -resistant C. albicans

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