4. Pharmacokinetic and Pharmacodynamic Characteristics of the Antifungal Agents Commonly Used for Treating Invasive Fungal Infections .
| drug class | application | pharmacokinetics | pharmacodynamics | central nervous system penetration | key efficacy | serious side effects |
|---|---|---|---|---|---|---|
| polyenes (amphotericin B) | topical | bioavailability (oral administration): low | concentration-dependent antifungal effect: yes | cerebrospinal fluid: low | Aspergillus spp., Blastomyces dermatitidis, Candida spp., C. immitis, C. neoformans, Histoplasma capsulatum, Mucor spp., Rhodotorula spp., Sporothrix schenckii | nephrotoxicity |
| oral | protein binding: high | prolonged post-antifungal effect: yes | brain tissue: low | |||
| intraperitoneal | metabolism (cytochrome P450): none | efficacy: concentration-dependent | ||||
| intravenous | excretion (unmetabolized): renal-low, hepatic-high | |||||
| distribution: plasma, extracellular fluids, outside the bloodstream | ||||||
| clearance: moderate | ||||||
| half-life: medium to long | ||||||
| time to maximum drug concentration: medium | ||||||
| triazoles (fluconazole, itraconazole, posaconazole, voriconazole, isavuconazole) | topical | bioavailability (oral administration): high | concentration-dependent antifungal effect: no | cerebrospinal fluid (%): low to high | Aspergillus spp., B. dermatitidis, Candida spp., C. immitis, C. neoformans, H. capsulatum, Paracoccidioides brasiliensis, Phaeohyphomycetes spp., S. schenckii | hepatotoxicity |
| oral | protein binding: low to high | prolonged post-antifungal effect: yes | brain tissue (%): high | |||
| intraperitoneal | metabolism (cytochrome P450): yes or glucuronidation | efficacy: exposition and minimum inhibitory concentration-dependent | ||||
| intravenous | excretion (unmetabolized): renal-medium to high, hepatic-low to high | |||||
| distribution: outside the bloodstream | ||||||
| clearance: high | ||||||
| half-life: medium to long | ||||||
| time to maximum drug concentration: short to medium | ||||||
| echinocandins (anidulafungin, caspofungin, micafungin) | intravenous | bioavailability (oral administration): orally not administered | concentration-dependent antifungal effect: yes | cerebrospinal fluid: low | Candida spp. | not known |
| protein binding: high | prolonged post-antifungal effect: yes | brain tissue: low to medium | ||||
| metabolism (cytochrome P450): yes, spontaneous degradation, independent | efficacy: exposition and (minimum inhibitory) concentration-dependent | |||||
| excretion (unmetabolized): renal-low, hepatic-low | ||||||
| distribution: plasma, extracellular fluids, outside the bloodstream | ||||||
| clearance: high | ||||||
| half-life: medium to long | ||||||
| time to maximum drug concentration: short to medium | ||||||
| flucytosine | oral | bioavailability (oral administration): high | concentration-dependent antifungal effect: no | cerebrospinal fluid: high | Candida spp., C. neoformans | nephrotoxicity, hepatotoxicity, bone marrow damage |
| intravenous | protein binding: low | prolonged post-antifungal effect: no | brain tissue: high | |||
| metabolism (cytochrome P450): minimal | efficacy: time-dependent | |||||
| excretion (unmetabolized): renal-high | ||||||
| distribution: plasma, extracellular fluids | ||||||
| clearance: moderate | ||||||
| half-life: short | ||||||
| time to maximum drug concentration: medium |
a
Compiled based on tables from Mazzei and Novelli, Lepak and Andes, Carmo et al., and Ashley.