ArticleAntimicrobial agents and chemotherapy2004
Pharmacodynamics of a new triazole, posaconazole, in a murine model of disseminated candidiasis.
Article in Antimicrobial agents and chemotherapy, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
76 citing papers in PubMed, 1 synthesis or guideline pooled it, 178 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
- Hypoalbuminemia and Posaconazole Therapeutic Drug Monitoring.Open forum infectious diseases · 2024Trial
- Pharmacokinetics of Intravenous Posaconazole in Critically Ill Patients.Antimicrobial agents and chemotherapy · 2018Trial
- Intrapulmonary pharmacokinetics and pharmacodynamics of posaconazole at steady state in healthy subjects.Antimicrobial agents and chemotherapy · 2009Trial
- Fluconazole MIC and the fluconazole dose/MIC ratio correlate with therapeutic response among patients with candidemia.Antimicrobial agents and chemotherapy · 2005Trial
- Posaconazole Target Attainment in Critically Ill Children: A 15-Year Single-Center Retrospective Analysis.Clinical and translational science · 2026Article
- Tea Saponins: a Novel Stabilizer for Enhancing the Oral Bioavailability of Albendazole Nanocrystals.AAPS PharmSciTech · 2025Article
- ISCCM Position Statement on the Management of Invasive Fungal Infections in the Intensive Care Unit.Indian journal of critical care medicine : peer-reviewed, official publication of Indian Society of Critical Care Medicine · 2024Article
- Preclinical Pharmacokinetic/Pharmacodynamic Studies and Clinical Trials in the Drug Development Process of EMA-Approved Antifungal Agents: A Review.Clinical pharmacokinetics · 2024Review
- Utilization of nanotechnology and experimental design in the development and optimization of a posaconazole‒calendula oil nanoemulgel for the treatment of mouth disorders.Frontiers in pharmacology · 2024Article
- Population Pharmacokinetics of Posaconazole in Immune-Compromised Children and Assessment of Target Attainment in Invasive Fungal Disease.Clinical pharmacokinetics · 2023Article
- In Vitro-In Vivo Correlation of Posaconazole-Amphotericin B Combination againstJournal of fungi (Basel, Switzerland) · 2023Article
- Postantifungal Effect of Antifungal Drugs againstJournal of fungi (Basel, Switzerland) · 2022Review
- Electromembrane Extraction of Posaconazole for Matrix-Assisted Laser Desorption/Ionization Mass Spectrometric Detection.Membranes · 2022Article
- Therapeutic Drug Monitoring of Antifungal Agents in Critically Ill Patients: Is There a Need for Dose Optimisation?Antibiotics (Basel, Switzerland) · 2022Review
- Article
- Model-Informed Drug Development for Anti-Infectives: State of the Art and Future.Clinical pharmacology and therapeutics · 2021Review
- The Role of New Posaconazole Formulations in the Treatment of Candida albicans Infections: Data from anAntimicrobial agents and chemotherapy · 2021Article
- Pharmacodynamics of Posaconazole in Experimental Invasive Pulmonary Aspergillosis: Utility of Serum Galactomannan as a Dynamic Endpoint of Antifungal Efficacy.Antimicrobial agents and chemotherapy · 2021Article
- Drug-Resistant Fungi: An Emerging Challenge Threatening Our Limited Antifungal Armamentarium.Antibiotics (Basel, Switzerland) · 2020Review
16 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Previous in vivo studies have characterized the pharmacodynamic characteristics of two triazole compounds, fluconazole and ravuconazole. These investigations demonstrated that the 24-h area under the concentration-time curve (AUC)/MIC ratio is the critical pharmacokinetic-pharmacodynamic (PK-PD) parameter associated with treatment efficacy. Further analysis demonstrated that a free-drug triazole 24-h AUC/MIC ratio of 20 to 25 was predictive of treatment success in both experimental models and clinical trials. We used a neutropenic murine model of disseminated Candida albicans infection to similarly characterize the time course activity of the new triazole, posaconazole. The PK-PD parameters (percent time above MIC, AUC/MIC ratio, and peak serum drug level/MIC ratio) were correlated with in vivo efficacy, as measured by organism number in kidney cultures after 48 h of therapy. Kinetics and protein binding following oral posaconazole dosing were performed in neutropenic infected mice. Peak levels and AUC from 0 h to infinity values were nonlinear over the 16-fold dose range studied. Serum drug elimination half-life ranged from 12.0 to 17.7 h. Protein binding was 99%. Single dose postantifungal effect studies demonstrated prolonged suppression of organism regrowth after serum posaconazole levels had fallen below the MIC. Treatment efficacy with the four dosing intervals studied was similar, supporting the AUC/MIC ratio as the PK-PD parameter predictive of efficacy. Nonlinear regression analysis also suggested that the AUC/MIC ratio was strongly predictive of treatment outcomes (AUC/MIC ratio R(2) = 83%; peak serum drug/MIC ratio R(2) = 85%; time that serum levels of posaconazole remained above the MIC R(2) = 65%). Similar studies were conducted with 11 additional C. albicans isolates with various posaconazole susceptibilities (MIC, 0.015 to 0.12 micro g/ml) to determine if a similar 24-h AUC/MIC ratio was associated with efficacy. The posaconazole free-drug AUC/MIC ratios were similar for all of the organisms studied (6.12 to 26.7, mean +/- SD = 16.9 +/- 7.8, P value, 0.42). These free-drug AUC/MIC ratios are similar to those observed for other triazoles in this model.
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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.