Voriconazole is the preferred treatment for invasive aspergillosis. Its mechanism differs from fluconazole in that voriconazole is active against Aspergillus because:

• A Voriconazole additionally inhibits ergosterol synthesis via squalene epoxidase in Aspergillus
• B Voriconazole has fungicidal rather than fungistatic activity against Aspergillus by disrupting cell wall glucan synthesis
• C Voriconazole inhibits CYP51 (lanosterol 14-alpha demethylase) in Aspergillus more potently due to its triazole side-chain modification ✓
• D Voriconazole has superior oral bioavailability (96%) compared to fluconazole (90%)

Explanation

Both fluconazole and voriconazole are azoles that inhibit fungal cytochrome P450 CYP51 (lanosterol 14-alpha demethylase), blocking ergosterol biosynthesis. Voriconazole's structural modification (fluorine substitution and alpha-methyl group on the propyl side-chain) dramatically enhances its binding to Aspergillus CYP51 compared to fluconazole, which has poor intrinsic activity against Aspergillus. Echinocandins (not azoles) inhibit beta-1,3-glucan synthesis; terbinafine inhibits squalene epoxidase.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.