Isavuconazonium is a second-generation triazole antifungal which is used to treat invasive aspergillosis and invasive mucormycosis. Due to low solubility in water of isavuconazole on its own, the isovuconazonium formulation is favorable as it has high solubility in water and allows for intravenous administration. This formulation also avoids the use of a cyclodextrin vehicle for solubilization required for intravenous administration of other antifungals such as voriconazole and posaconazole, eliminating concerns of nephrotoxicity associated with cyclodextrin. Isavuconazonium disrupts the biosynthesis of ergosterol, which is a key component of fungal cell membrane. It inhibits cytochrome P-450 dependent enzyme lanosterol 14-alpha-demethylase (sterol 14-α-demethylase) that mediates the conversion of lanosterol to ergosterol. As a result of lanosterol 14-alpha-demethylase inhibition, toxic methylated sterol precursors such as 14-α-methylated lanosterol, 4,14-dimethylzymosterol, and 24-methylenedihydrolanosterol alter the function of fungal membrane and accumulate within the fungal cytoplasm. Depletion of ergosterol within the fungal cell membrane leads to decreased structural integrity and function of the cell membrane, inhibited fungal cell growth and replication, and ultimately cell death.

Isavuconazonium Pathway References