Determination of Pharmacodynamic Target Exposures for Rezafungin against Candida tropicalis and Candida dubliniensis in the Neutropenic Mouse Disseminated Candidiasis Model

Rezafungin (CD101) is a novel echinocandin under development for once-weekly intravenous (i.v.) dosing. We evaluated the pharmacodynamics (PD) of rezafungin against 4 and 4 strains, using the neutropenic mouse invasive candidiasis model. The area under the concentration-time curve (AUC)/MIC was a ro...

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Published inAntimicrobial agents and chemotherapy Vol. 63; no. 11
Main Authors Lepak, Alexander J, Zhao, Miao, Andes, David R
Format Journal Article
LanguageEnglish
Published United States American Society for Microbiology 01.11.2019
Subjects
Experimental Therapeutics
Candida tropicalis
rezafungin
pharmacodynamics
echinocandin
Candida dubliniensis
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Summary:Rezafungin (CD101) is a novel echinocandin under development for once-weekly intravenous (i.v.) dosing. We evaluated the pharmacodynamics (PD) of rezafungin against 4 and 4 strains, using the neutropenic mouse invasive candidiasis model. The area under the concentration-time curve (AUC)/MIC was a robust predictor of efficacy ( = 0.93 and 0.72, respectively). The stasis free-drug 24-h AUC/MIC target exposure for the group ranged from 3 to 25, whereas the 1-log-kill free-drug 24-h AUC/MIC target exposure ranged from 4.3 to 62. These values are similar to those found in previous rezafungin PD studies with other spp. Based on recent surveillance susceptibility data, AUC/MIC targets are likely to be exceeded for >99% of and isolates with the previously studied human dose of 400 mg i.v. once weekly.
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ISSN:0066-4804
1098-6596
DOI:10.1128/AAC.01556-19