Pharmacological basis of CD101 efficacy: exposure shape matters
Open accessAbstract
CD101 is a novel echinocandin with concentration-dependent fungicidal activity in vitro and a long half-life (∼133 h in humans, ∼70 to 80 h in mice). Given these characteristics, it is likely that the shape of the CD101 exposure (i.e., the time course of CD101 concentrations) influences efficacy. To test this hypothesis, doses which produce the same total area under the concentration-time curve (AUC) were administered to groups of neutropenic ICR mice infected with Candida albicans R303 using three different schedules. A total CD101 dose of 2 mg/kg was administered as a single intravenous (i.v.) dose or in equal divided doses of either 1 mg/kg twice weekly or 0.29 mg/kg/day over 7 days. The studies were performed using a murine disseminated candidiasis model. Animals were euthanized at 168 h following the start of treatment. Fungi grew well in the no-treatment control group and showed variable changes in fungal density in the treatment groups. When the CD101 AUC from 0 to 168 h (AUC 0–168 ) was administered as a single dose, a >2 log 10 CFU reduction from the baseline at 168 h was observed. When twice-weekly and daily regimens with similar AUC values were administered, net fungal stasis and a >1 log 10 CFU increase from the baseline were observed, respectively. These data support the hypothesis that the shape of the CD101 AUC influences efficacy. Thus, CD101 administered once per week demonstrated a greater degree of fungal killing than the same dose divided into twice-weekly or daily regimens.
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Rezafungin has a prolonged half-life of around 133 h that allows extended-interval dosing and provides high plasma drug concentrations early in therapy.
“Rezafungin has a prolonged half-life (around 133 h) that allows extended-interval dosing and provides high plasma drug concentrations early in therapy.”
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- Authors
- Lakota, E. A., Bader, J. C., Ong, V., Bartizal, K., Miesel, L., Andes, D. R., Bhavnani, S. M., Rubino, C. M., Ambrose, P. G., & Lepak, A. J.
- Affiliations
- Institute for Clinical Pharmacodynamics (United States) (US)
- Cidara Therapeutics (United States) (US)
- Eurofins (United States) (US)
- University of Wisconsin–Madison (US)
- Corresponding author
- Lakota, Elizabeth A.
- ORCID
- Venue
- Antimicrobial Agents and Chemotherapy
- Publisher
- American Society for Microbiology
- Published
- 2017-11
- Volume
- 61
- Issue
- 11
- ISSN
- 0066-4804 (ISSN-L)
- 1098-6596
- PMC
- PMC5655053
- OpenAlex
- W2749642217
- Cited by
- 40
- References
- 14
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 4 · 2023: 3 · 2022: 5 · 2021: 4 · 2020: 4 · 2019: 4 · 2018: 6 · 2017: 3
- FWCI
- 3.58
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Antimicrobial Agents and Chemotherapy (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Health Sciences › Medicine › Pharmacology › Antibiotics Pharmacokinetics and Efficacy
- Health Sciences › Medicine › Epidemiology › Fungal Infections and Studies
- Keywords
- CD101, echinocandins, Candida albicans, systemic candidiasis, dosing regimen, area under the curve, single-dose administration, twice-weekly dosing, daily dosing, antifungal efficacy, neutropenic mice, fungal load
- MeSH terms
- Animals, Antifungal Agents, Candida albicans, Candidiasis, Disease Models, Animal, Drug Administration Schedule, Humans, Mice, Inbred ICR, Microbial Sensitivity Tests, Mice, Echinocandins
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