Novel and emerging pharmacotherapy and device-based treatments for onychomycosis
Robert Baran, Dimitris Rigopoulos, Chander Grover, Eckart Haneke in Nail Therapies, 2021
Albaconazole is an investigational triazole that is effective against a broad spectrum of dermatophyte and yeast species. It has a long half-life, which allows for once weekly dosage. In a phase II study, 54% of the patients treated with albaconazole once weekly for 36 weeks had a mycologic cure at week 52 with a favorable safety profile. Therefore, it may be an alternative to existing systemic therapies for distal subungual onychomycosis in the future.
Albaconazole
M. Lindsay Grayson, Sara E. Cosgrove, Suzanne M. Crowe, M. Lindsay Grayson, William Hope, James S. McCarthy, John Mills, Johan W. Mouton, David L. Paterson in Kucers’ The Use of Antibiotics, 2017
Albaconazole (UR-9825) is a new triazole (Figure 159.1) with a potent broad spectrum of antifungal activity, favorable pharmacokinetics, and high oral bioavailability (Ramos et al., 1999; Capilla et al., 2001; Alves et al., 2006; Pasqualotto and Denning, 2008). Its in vitro activity against Scedosporium prolificans and Paecilomyces distinguishes it from other new triazoles.
Oral antifungal therapies for toenail onychomycosis: a systematic review with network meta-analysis toenail mycosis: network meta-analysis
Published in Journal of Dermatological Treatment, 2022
Maria L. D. Fávero, Aline F. Bonetti, Eric L. Domingos, Fernanda S. Tonin, Roberto Pontarolo
The second-generation azoles have broad-spectrum antifungal activity, both for superficial and invasive infections, acting as reversible inhibitors of the sterol enzyme of P450 cytochrome (67). Albaconazole has good pharmacokinetic and bioavailability properties with a long half-life that allows for weekly dosing schedules (15,68). This has the potential to improve patient compliance to treatment, particularly with long courses therapies. The effects of albaconazole are dose-dependent, as demonstrated in our network meta-analysis, where higher cure rates were obtained with higher doses of albaconazole. Concerning safety, we found that albaconazole was more prone to causing gastrointestinal events, such as nausea and diarrhea. However, it seems that this drug is well-tolerated, with treatment-related adverse events occurring in less than 3% of patients, all with mild-moderated severity (15). Posaconazole at 200 and 400 mg is significantly associated with complete cure in long-term treatments (over 48 weeks) when compared to terbinafine (35); however, higher doses were more related to discontinuation due adverse events, which may prevent its broad use in practice.
Synthesis of novel pyrroles and fused pyrroles as antifungal and antibacterial agents
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2021
Rania Helmy Abd El-Hameed, Amira Ibrahim Sayed, Shima Mahmoud Ali, Mohamed A. Mosa, Zainab M. Khoder, Samar Said Fatahala
Another major cause of OIs and the consequent fatality is the fungal pathogens. The most common opportunistic fungi include Candida species, Aspergillus species, and Fusarium species5. Candida species, was a major cause of morbidity and mortality worldwide over the past few decades6. Aspergillus fumigatus (A. fumigatus) is a saprophyte that has become the most prevalent airborne fungal pathogen7. A. fumigatus causes severe and usually fatal invasive aspergillosis in immuno-compromised hosts in developed countries7. The members of Fusarium oxysporum (F. oxysporum) complex, (FOSC) are soil borne pathogens that cause diseases to a broad range of important crops with a number of them having the ability to cause human diseases that can be fatal8. Because fungi are eukaryotes, they have similarities with mammalian cells making it difficult to design a drug with selective toxicity9. The first antifungal drug discovered was amphotericin B10 followed by flucytosine11, later on two imidazole derivatives, clotrimazole and miconazole, were extensively used in treatment of fungal infections12–15. Triazole derivative, fluconazole, is an antifungal agent with low toxicity and high antifungal activity16. Resistance of some fungi against imidazole is now becoming a serious clinical problem17, several azole-related adverse drug effects (ADEs) are now considered such as hepatotoxicity and cardiac effects. In order to enrich the antifungal activity and/or diminish antifungal ADEs, new derivatives were synthesised containing other heterocycles instead of imidazole and 1,2,4-triazole, such as indole, 1,2,3-triazoles14,18–20. Voriconazole is a clinically important triazoles antifungal containing fluoropyrimidine13,20. Using quinazoline ring instead of a triazole ring results in albaconazole with higher in vitro activity than fluconazole21. Itraconazole with piperazinyl phenyl side chain showed remarkable in vitro antifungal activity against several pathogenic fungi16, as shown in Figure 1.
Related Knowledge Centers
- Triazole
- Cytochrome P450
- Antiprotozoal