Antifungal drugs combinations: a patent review 2000-2015

Expert Opinion on Therapeutic Patents
Laura A SvetazMaximiliano A Sortino

Abstract

Combination therapy has emerged as an approach to improve the efficacy of antifungal drugs. Its main objective is to achieve synergistic interaction with higher antifungal properties and lower toxic effects than each substance alone. Twenty-four patents disclosed in the period of 2000-2015 were covered in this review. Twenty of them were devoted to pharmacodynamic potentiation, while four were dedicated to pharmacokinetic actions. The common characteristic of most patents published in this area is that the main partner is a commercial antifungal drug. In the most innovative combinations the second component was either a modifier of proton homeostasis, an antibody, an inhibitor of the adhesion of epithelial or endothelial cells or a keratinolytic agent that improves the skin penetration. The evaluation of synergism is always made with simple in vitro methods, which constitutes a weakness of the disclosed patents, due to the lack of in vivo studies, since the in vitro tests cannot predict the in vivo behavior. Also, it is surprising that none of the patents analyze the toxicity of the new combinations, taking into account that one of the main objectives of the combinations is to reduce the toxicity of the existing antifungal drugs.

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Citations

May 11, 2016·Journal of Enzyme Inhibition and Medicinal Chemistry·Simone CarradoriLetizia Angiolella
Nov 5, 2016·Diagnostic Microbiology and Infectious Disease·Janaína de Cássia Orlandi SardiMaria José Soares Mendes-Giannini
Oct 18, 2016·Journal of Pharmaceutical and Biomedical Analysis·Petra FürediImre Klebovich
Nov 30, 2016·Expert Opinion on Therapeutic Patents·María Victoria CastelliSilvia Noelí López
Jan 19, 2020·Pharmacology & Therapeutics·Alireza TavakkoliAmirhossein Sahebkar

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