In Vivo Pharmacodynamic Target Investigation for Micafungin against Candida albicans and C. glabrata in a Neutropenic Murine Candidiasis Model
Open accessAbstract
Previous studies using in vivo candidiasis models have demonstrated that the concentration-associated pharmacodynamic indices, the maximum concentration of a drug in serum/MIC and 24-h area under the curve (AUC)/MIC, are associated with echinocandin treatment efficacy. The current investigations used a neutropenic murine model of disseminated Candida albicans and C. glabrata infection to identify the 24-h AUC/MIC index target associated with a stasis and killing endpoint for the echinocandin, micafungin. The kinetics after intraperitoneal micafungin dosing were determined in neutropenic infected mice. Peak levels and AUC values were linear over the 16-fold dose range studied. The serum drug elimination half-life ranged from 7.5 to 16 h. Treatment studies were conducted with 4 C. albicans and 10 C. glabrata isolates with micafungin MICs varying from 0.008 to 0.25 μg/ml to determine whether similar 24-h AUC/MIC ratios were associated with efficacy. The free drug AUC/MICs associated with stasis and killing (1-log) endpoints were near 10 and 20, respectively. The micafungin exposures associated with efficacy were similar for the two Candida species. Furthermore, the free drug micafungin exposures required to produce stasis and killing endpoints were similar to those recently reported for another echinocandin, anidulafungin, against the identical Candida isolates in this model.
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PK/PD studies with echinocandins demonstrate concentration-dependent activity with a prolonged PAFE similar to that observed with amphotericin B.
“PK/PD studies with the echinocandin class of antifungals demonstrate concentrationdependent activity with a prolonged PAFE similar to that observed with amphotericin B.”
From Fungal Sepsis: Optimizing Antifungal Therapy in the Critical Care Setting (2011) · cites this paper as [158]
The concentration-dependent indices Cmax/MIC and AUC/MIC are both closely linked to efficacy for echinocandins and support administration of large infrequent doses.
“The concentration-dependent indices, C max /MIC and AUC/MIC, are both closely linked to efficacy and support administration of large infrequent doses.”
From Fungal Sepsis: Optimizing Antifungal Therapy in the Critical Care Setting (2011) · cites this paper as [158]
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- Authors
- Andes, D. R., Diekema, D. J., Pfaller, M. A., Marchillo, K., & Bohrmueller, J.
- Affiliations
- University of Wisconsin–Madison (US)
- University of Iowa (US)
- Department of Medicine
- Corresponding author
- Andes, D. R.
- Venue
- Antimicrobial Agents and Chemotherapy
- Publisher
- American Society for Microbiology
- Published
- 2008-10
- Volume
- 52
- Issue
- 10
- Pages
- 3497-3503
- ISSN
- 0066-4804 (ISSN-L)
- 1098-6596
- PMC
- PMC2565916
- OpenAlex
- W2147530964
- Cited by
- 134
- References
- 48
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 5 · 2023: 5 · 2022: 2 · 2021: 6 · 2020: 6 · 2019: 4 · 2018: 6 · 2017: 11 · 2016: 11 · 2015: 10 · 2014: 8 · 2013: 5 · 2012: 5
- FWCI
- 9.48
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Antimicrobial Agents and Chemotherapy (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Astellas Pharma
- 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
- micafungin, echinocandins, Candida albicans, Candida glabrata, therapeutic target, AUC/MIC ratio, drug exposure, antifungal efficacy, pharmacokinetics, elimination half-life, anidulafungin, systemic candidiasis
- MeSH terms
- Micafungin, Animals, Antifungal Agents, Candida albicans, Candidiasis, Disease Models, Animal, Female, Mice, Inbred ICR, Neutropenia, Colony Count, Microbial, Candida glabrata, Mice, Echinocandins, Lipopeptides
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