Table 2.

Principle properties of selected antifungal drugs used for treatment of central nervous system infections [1, 3, 39, 54, 80, 123, 124, 130, 133]

Antifungal agent	Selected pharmacokinetics properties	Mode of action	Spectrum of activity
Amphotericin B (Polyene antibiotic) Amphotericin B formulations  Deoxycholate—AmBd  Lipid complex—ABLC  Colloidal dispersion—ABCD  Liposomal—L-AmB	Concentration-dependent pharmacokinetics—for all formulations Plasma protein binding—95–99%—for all formulations T1/2 of AmBd of 15–27 h T1/2 of ABLC of ~ 24 h T1/2 of L-AmB of 12–24 h T1/2 of ABCD of ~ 18 h Vd (L/kg) of AmBd—0.5–2.0 Vd (L/kg) of L-AmB—0.05–2.2	Binding and interaction with ergosterol and destabilization of fungal cell membrane; increase in cell membrane permeability for mono- and divalent cations, which leads to cell death	Mucor Absidia Aspergillus Cryptococcus Candida Histoplasma Blastomyces Coccidioides Paracoccidioides Sporothrix
Fluconazole (Triazole)	Dose-proportional pharmacokinetics (except in patients with renal impairment) Plasma protein binding—12% T1/2 of 24–30 h Vd (L/kg)—0.7	Inhibition of cytochrome P-450 14 α-lanosterol demethylase; accumulation of lanosterol leading to disorders in the cell membrane	Candida (except C. glabrata and C. krusei) Cryptococcus Histoplasma Blastomyces Coccidioides
Itraconazole (Triazole)	Concentration-dependent pharmacokinetics Plasma protein binding 99.8% T1/2 of 34 h Vd (L/kg)—11	Inhibition of ergosterol synthesis in the fungal cell membrane like other triazoles	Aspergillus Cryptococcus Candida Histoplasma Paracoccidioides Blastomyces Sporothrix
Voriconazole (Triazole)	Concentration-dependent pharmacokinetics Plasma protein binding—58% T1/2 of ~ 6 h Vd (L/kg)—45	The mechanism of action on fungi is similar for fluconazole	Candida Aspergillus Fusarium Scedosporium
Posaconazole (Triazole)	Dose-proportional pharmacokinetics Plasma protein binding > 98% T1/2 of 20–31 h Vd (L/kg)—20 (oral suspension) Vd (L/kg)—5 (tablet formulation) Vd (L/kg)—3.7 (intravenous)	Fungicidal action similar to other triazoles	Aspergillus Candida Coccidioides Fusarium Rhizomucor Mucor Rhizopus
Isavuconazole (Triazole)	Dose-proportional pharmacokinetics Plasma protein binding > 98% T1/2 of 80–120 h Vd (L/kg)—65	The mechanism of action on fungi is similar for fluconazole	Candida Aspergillus Mucor Rhizopus Rhizomucor Fusarium Sporothrix
Flucytosine/5-FC/(Nucleoside)	Dose-proportional pharmacokinetics (except in patients with renal impairment) Plasma protein binding—5% T1/2 of 3–5 h Vd (L/kg)—0.4–0.8	Weakening of nucleic acid synthesis by formation of toxic, fluorine pyrimidine antimetabolites It enters the fungal cell by cytosine permease where it is deaminated to the active form of 5-fluorocytosine, which weakens the synthesis of DNA and RNA	Cryptococcus Candida Cladophialophora Fonsecaea Phialophora

Vd apparent volume of distribution, T_1/2 half-life