ArticleAntimicrobial agents and chemotherapy2008
In vivo pharmacodynamic characterization of anidulafungin in a neutropenic murine candidiasis model.
Article in Antimicrobial agents and chemotherapy, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers, 1 of them a synthesis that pooled it.
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Who cites it
59 citing papers in PubMed, 1 synthesis or guideline pooled it, 140 citations in OpenAlex.
- Antifungal pharmacodynamics: Latin America's perspective.The Brazilian journal of infectious diseases : an official publication of the Brazilian Society of Infectious DiseasesPooled it
- Pharmacokinetic Properties of Micafungin in Critically Ill Patients Diagnosed with Invasive Candidiasis.Antimicrobial agents and chemotherapy · 2017Trial
- Safety and Pharmacokinetics of CD101 IV, a Novel Echinocandin, in Healthy Adults.Antimicrobial agents and chemotherapy · 2017Trial
- Clinical pharmacodynamic index identification for micafungin in esophageal candidiasis: dosing strategy optimization.Antimicrobial agents and chemotherapy · 2013Trial
- Anidulafungin exposure and population pharmacokinetics in critically ill patients with invasive candidiasis.Infection · 2025Observational
- Preclinical Pharmacokinetic/Pharmacodynamic Studies and Clinical Trials in the Drug Development Process of EMA-Approved Antifungal Agents: A Review.Clinical pharmacokinetics · 2024Review
- Postantifungal Effect of Antifungal Drugs againstJournal of fungi (Basel, Switzerland) · 2022Review
- Pharmacokinetic/Pharmacodynamic Target Attainment of Different Antifungal Agents in De-escalation Treatment in Critically Ill Patients: a Step toward Dose Optimization Using Monte Carlo Simulation.Antimicrobial agents and chemotherapy · 2022Article
- Therapeutic Drug Monitoring of Antifungal Agents in Critically Ill Patients: Is There a Need for Dose Optimisation?Antibiotics (Basel, Switzerland) · 2022Review
- DectiSomes: Glycan Targeting of Liposomal Drugs Improves the Treatment of Disseminated Candidiasis.Antimicrobial agents and chemotherapy · 2022Article
- Precision Therapy for Invasive Fungal Diseases.Journal of fungi (Basel, Switzerland) · 2021Article
- Repositioning Lopinavir, an HIV Protease Inhibitor, as a Promising Antifungal Drug: Lessons Learned fromJournal of fungi (Basel, Switzerland) · 2021Article
- Model-Informed Drug Development for Anti-Infectives: State of the Art and Future.Clinical pharmacology and therapeutics · 2021Review
- Role and Interpretation of Antifungal Susceptibility Testing for the Management of Invasive Fungal Infections.Journal of fungi (Basel, Switzerland) · 2020Review
- Rezafungin-Mechanisms of Action, Susceptibility and Resistance: Similarities and Differences with the Other Echinocandins.Journal of fungi (Basel, Switzerland) · 2020Review
- Administration and Dosing of Systemic Antifungal Agents in Pediatric Patients.Paediatric drugs · 2020Review
- Extended-Interval Dosing of Rezafungin against Azole-Resistant Aspergillus fumigatus.Antimicrobial agents and chemotherapy · 2019Article
- A quantitative systems pharmacology (QSP) model for Pneumocystis treatment in mice.BMC systems biology · 2018Article
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Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Multiple in vivo studies have characterized the pharmacodynamics of drugs from the triazole and polyene antifungal drug classes. Fewer studies have investigated these pharmacodynamic relationships for the echinocandin drug class. We used a neutropenic murine model of disseminated Candida albicans, Candida tropicalis, and Candida glabrata infection to characterize the time course of activity of the new echinocandin anidulafungin. The pharmacokinetic-pharmacodynamic (PK-PD) indices (the percentage of time that the drug concentration was above the MIC, the ratio of the area under the concentration-time curve from 0 to 24 h [AUC(0-24)] to the MIC, and the ratio of the maximum serum drug concentration [C(max)] to the MIC) were correlated with in vivo efficacy, as measured by organism numbers in kidney cultures after 96 h of therapy. The kinetics following intraperitoneal anidulafungin dosing in neutropenic infected mice were monitored. Peak levels and AUCs were linear over the 16-fold dose range studied. The drug elimination half-life in serum ranged from 14 to 24 h. Single-dose postantifungal-effect studies demonstrated prolonged suppression of organism regrowth after serum anidulafungin levels had fallen below the MIC. Of the four dosing intervals studied, treatment with the more widely spaced dosing regimens was most efficacious, suggesting the C(max)/MIC ratio as the PK-PD index most predictive of efficacy. Nonlinear regression analysis suggested that both the C(max)/MIC and AUC/MIC ratios were strongly predictive of treatment success. Studies were then conducted with 13 additional C. albicans, C. tropicalis, and C. glabrata isolates with various anidulafungin susceptibilities (MICs of anidulafungin for these strains, 0.015 to 2.0 microg/ml) to determine if similar C(max)/MIC and AUC(0-24)/MIC ratios for these isolates were associated with efficacy. The anidulafungin exposures associated with efficacy were similar among Candida species.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.