Pharmacodynamics of the Novel Antifungal Agent F901318 for Acute Sinopulmonary Aspergillosis Caused by Aspergillus flavus

• Autor(a) principal: Negri, Clara Ezequiel [UNIFESP]
• Data de Publicação: 2018
• Outros Autores: Johnson, Adam, McEntee, Laura, Box, Helen, Whalley, Sarah, Schwartz, Julie A., Ramos-Martin, V., Livermore, Joanne, Kolamunnage-Dona, Ruwanthi, Colombo, Arnaldo Lopes [UNIFESP], Hope, William W.
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Institucional da UNIFESP
• Texto Completo: https://repositorio.unifesp.br/handle/11600/55775; http://dx.doi.org/10.1093/infdis/jix479
• topic: Aspergillus flavus; in vivo; orotomides; pharmacodynamics; pharmacokinetics

Background. Aspergillus flavus is one of the most common agents of invasive aspergillosis and is associated with high mortality. The orotomides are a new class of antifungal agents with a novel mechanism of action. An understanding of the pharmacodynamics (PD) of the lead compound F901318 is required to plan safe and effective regimens for clinical use. Methods. The pharmacokinetics (PK) and PD of F901318 were evaluated by developing new in vitro and in vivo models of invasive fungal sinusitis. Galactomannan was used as a pharmacodynamic endpoint in all models. Mathematical PK-PD models were used to describe dose-exposure-response relationships. Results. F901318 minimum inhibitory concentrations (MICs) ranged from 0.015 to 0.06 mg/L. F901318 induced a concentration-dependent decline in galactomannan. In the in vitro model, a minimum concentration: MIC of 10 resulted in suppression of galactomannan