Antifungal Drugs
Abstract
1. Introduction
2. Overview of Antifungal Agents and Their Mechanisms of Action
3. Pharmacology and Toxicity of Antifungal Agents
4. Susceptibility of Antifungal Agents
5. Resistance to Antifungal Agents
6. The Antifungal Pipeline
Author Contributions
Funding
Conflicts of Interest
References
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Triazole | FLC [32] | ITC [33] | VOR [34] | POS [35] | ISV [36] |
---|---|---|---|---|---|
Bioavailability [%] | 90 | 55 | 90–96 | variable | >98 |
Protein binding [%] | 11–12 | 99 | 51–67 | >98 | >99 |
Metabolism (CYP) | – | 3A4 | 2C19/2C9/3A4 | glucuronidation | 3A4/3A5 |
Half-life [h] | 27–37 | 15–42 | 6 | 15–35 | 80–130 |
Route of elimination | renal | hepatic | hepatic | hepatic | hepatic |
Unchanged [%] | 64–90 | 3–18 | <2 | 66 | 45 |
Echinocandin | ANF [38,39] | CSF [38,40] | MCF [38,41] |
---|---|---|---|
Bioavailability [%] | 2–7 (p.o.), 100 (iv.) | 100 (iv.) | 100 (iv.) |
Protein binding [%] | 99 | 95 | >99 |
Metabolism (CYP) | – | – | 3A |
Half-life [h] | 40–50 | 8 | 13–20 |
Route of elimination | hepatic | renal | hepatic |
Unchanged [%] | 10 | 1.4 | <1 |
Population | Neonatals (IC) [42] | Neonatals (IA) [43] | Children (IC) [48] | Children (IA) [43] | Adults (IC) [44] | HSCT (IA) [45] | CMTH (IA) [45] | NN (IA) [45] | NH (IA) [45] |
---|---|---|---|---|---|---|---|---|---|
AMBD | 0.5–1.5 | 1.0–1.5 | 0.6–1.5 | 1.0–1.5 | note 1 | note 1 | note 1 | note 1 | note 2 |
ABCD | 3–5 | note 1 | note 1 | note 1 | note 1 | note 1 | note 1 | note 1 | note 2 |
ABLC | 5 | 5 | 1–5 | 5 | note 1 | note 1 | note 1 | note 1 | note 2 |
LAMB | 1–5 | 3 | 1–5 | 3 | 3 | 3 | 3 | 3 | note 1 |
5-FC | 100 | note 2 | 25–100 | note 2 | note 2 | note 2 | note 2 | note 2 | note 2 |
FLC | 12 | note 2 | 6–12 | note 2 | note 1 | note 2 | note 2 | note 2 | note 2 |
ITC | note 2 | note 3 | 5–10 | 10 | note 1 | note 2 | note 1 | note 2 | note 2 |
VOR | note 3 | note 3 | 8–16 | 8–16 | 3–6 | note 1 | note 1 | note 1 | note 1 |
POS | note 2 | note 3 | note 3 | note 3 | note 1 | 2–12 | 8–12 | 2–12 | note 1 |
ISV | note 1 | note 2 | note 2 | note 2 | note 2 | note 2 | note 2 | note 2 | note 2 |
ANF | 1.5 | note 1 | note 3 | note 1 | 100–200 4 | note 1 | note 2 | note 1 | note 2 |
CSF | 0.5–2 | 25–70 5 | 50–70 5 | 50–70 5 | 50–70 4 | note 1 | 70 5 | note 1 | note 1 |
MCF | 4–15 | note 3 | 2–4 | note 3 | 100 4 | note 1 | 100 4 | note 1 | note 2 |
AA | MIC90 [mg/L] | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Aspergillus | ||||||||||
flavus | fumigatus | nidulans | niger | terreus | ||||||
S≤ | R> | S≤ | R> | S≤ | R> | S≤ | R> | S≤ | R> | |
AMB | – | – | 1 | 1 | – | – | 1 | 1 | – | – |
ANF | IE | IE | IE | IE | IE | IE | IE | IE | IE | IE |
CSF | IE | IE | IE | IE | IE | IE | IE | IE | IE | IE |
FLC | – | – | – | – | – | – | – | – | – | – |
ISV | 1 | 2 | 1 | 2 | 0.25 | 0.25 | IE | IE | 1 | 1 |
ITC | 1 | 1 | 1 | 1 | 1 | 1 | IE | IE | 1 | 1 |
MCF | IE | IE | IE | IE | IE | IE | IE | IE | IE | IE |
POS | IE | IE | 0.125 | 0.25 | IE | IE | IE | IE | 0.125 | 0.25 |
VOR | IE | IE | 1 | 1 | 1 | 1 | IE | IE | IE | IE |
AA | MIC90 [mg/L] | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
Candida | ||||||||||||
albicans | dubliniensis | glabrata | krusei | parapsilosis | tropicalis | |||||||
S≤ | R> | S≤ | R> | S≤ | R> | S≤ | R> | S≤ | R> | S≤ | R> | |
AMB | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 |
ANF | 0.03 | 0.03 | – | – | 0.06 | 0.06 | 0.06 | 0.06 | 4 | 4 | 0.06 | 0.06 |
CSF 1 | – | – | – | – | – | – | – | – | – | – | – | – |
FLC | 2 | 4 | 2 | 4 | 0.001 | 16 | IE | IE | 2 | 4 | 2 | 4 |
ISV | IE | IE | IE | IE | IE | IE | IE | IE | IE | IE | IE | IE |
ITC | 0.06 | 0.06 | 0.06 | 0.06 | IE | IE | IE | IE | 0.125 | 0.125 | 0.125 | 0.125 |
MCF | 0.016 | 0.016 | – | – | 0.03 | 0.03 | IE | IE | 2 | 2 | IE | IE |
POS | 0.06 | 0.06 | 0.06 | 0.06 | IE | IE | IE | IE | 0.06 | 0.06 | 0.06 | 0.06 |
VOR | 0.06 | 0.25 | 0.06 | 0.25 | IE | IE | IE | IE | 0.125 | 0.25 | 0.125 | 0.25 |
AA | Identification | Last Update | Phase 0 | Phase 1 | Phase 2 | Phase 3 | Phase 4 |
---|---|---|---|---|---|---|---|
VT-1129 [79] | – | – | |||||
VT-1161 [80] | NCT03562156 | 5th Feb 2020 | |||||
VT-1598 [81] | – | – | |||||
PC1244 [82] | – | – | |||||
SUBA-ITC [80] | NCT03572049 | 25th Oct 2019 | |||||
CAMB [80] | NCT02971007 | 2nd Nov 2018 | |||||
Rezafungin [80] | NCT03667690 | 5th Feb 2020 | |||||
Ibrexafungerp [80] | NCT03363841 | 2nd Dec 2019 | |||||
Fosmanogepix [80] | NCT03604705 | 28th Feb 2020 | |||||
Olorofim [80] | NCT03583164 | 18th Jan 2020 | |||||
MGCD290 [80] | NCT01497223 | 4th April 2013 | |||||
T-2307 [83] | – | – | |||||
VL-2397 [80] | NCT03327727 | 27th Feb 2019 |
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Houšť, J.; Spížek, J.; Havlíček, V. Antifungal Drugs. Metabolites 2020, 10, 106. https://doi.org/10.3390/metabo10030106
Houšť J, Spížek J, Havlíček V. Antifungal Drugs. Metabolites. 2020; 10(3):106. https://doi.org/10.3390/metabo10030106
Chicago/Turabian StyleHoušť, Jiří, Jaroslav Spížek, and Vladimír Havlíček. 2020. "Antifungal Drugs" Metabolites 10, no. 3: 106. https://doi.org/10.3390/metabo10030106
APA StyleHoušť, J., Spížek, J., & Havlíček, V. (2020). Antifungal Drugs. Metabolites, 10(3), 106. https://doi.org/10.3390/metabo10030106