Trial reportThe Journal of antimicrobial chemotherapy2016
Pharmacodynamics of isavuconazole in experimental invasive pulmonary aspergillosis: implications for clinical breakpoints.
Trial report in The Journal of antimicrobial chemotherapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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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.
The trial behind it
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.
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Who cites it
22 citing papers in PubMed, 32 citations in OpenAlex.
- Exposure-Response Relationships for Isavuconazole in Patients with Invasive Aspergillosis and Other Filamentous Fungi.Antimicrobial agents and chemotherapy · 2017Trial
- Population pharmacokinetics, target attainment and individualized dosing of isavuconazole in critically ill adults receiving extracorporeal membrane oxygenation.JAC-antimicrobial resistance · 2026Article
- Characterization of isavuconazole pharmacokinetics and pharmacodynamics in a real-life cohort.JAC-antimicrobial resistance · 2026Article
- Exploratory model-based optimizing isavuconazole dosing regimens forFrontiers in cellular and infection microbiology · 2026Article
- Therapeutic Drug Monitoring and Biomarkers; towards Better Dosing of Antimicrobial Therapy.Pharmaceutics · 2024Article
- Long-Term Kinetics of Serum Galactomannan during Treatment of Complicated Invasive Pulmonary Aspergillosis.Journal of fungi (Basel, Switzerland) · 2023Article
- New Perspectives on Antimicrobial Agents: Isavuconazole.Antimicrobial agents and chemotherapy · 2022Review
- Population Pharmacokinetics and Pharmacodynamic Target Attainment of Isavuconazole againstPharmaceutics · 2021Article
- Efficacy and Associated Drug Exposures of Isavuconazole and Fluconazole in an Experimental Model of Coccidioidomycosis.Antimicrobial agents and chemotherapy · 2021Article
- Modeling Invasive Aspergillosis: How Close Are Predicted Antifungal Targets?Journal of fungi (Basel, Switzerland) · 2020Review
- A Mortality Prediction Rule for Hematology Patients with Invasive Aspergillosis Based on Serum Galactomannan Kinetics.Journal of clinical medicine · 2020Article
- Influence of Sustained Low-Efficiency Dialysis Treatment on Isavuconazole Plasma Levels in Critically Ill Patients.Antimicrobial agents and chemotherapy · 2019Article
- Interlaboratory Analysis of Isavuconazole Plasma Concentration Assays Among European Laboratories.Therapeutic drug monitoring · 2019Article
- Isavuconazole Kinetic Exploration for Clinical Practice.Drugs in R&D · 2018Article
- Clinical Pharmacokinetics and Pharmacodynamics of Isavuconazole.Clinical pharmacokinetics · 2018Review
- Animal Models of Aspergillosis.Comparative medicine · 2018Review
- Combination Therapy with Isavuconazole and Micafungin for Treatment of Experimental Invasive Pulmonary Aspergillosis.Antimicrobial agents and chemotherapy · 2017Article
- Pharmacodynamics of the Orotomides againstmBio · 2017Article
- Prognostic value of galactomannan: current evidence for monitoring response to antifungal therapy in patients with invasive aspergillosis.Journal of pharmacokinetics and pharmacodynamics · 2017Review
- Successful Treatment of Allergic Bronchopulmonary Aspergillosis With Isavuconazole: Case Report and Review of the Literature.Open forum infectious diseases · 2017Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectivesIsavuconazole, a novel triazole antifungal agent, has broad-spectrum activity against Aspergillus spp. and other pathogenic fungi. The isavuconazole exposure-response relationship in experimental invasive pulmonary aspergillosis using galactomannan index (GMI) suppression as a marker of disease clearance was explored.
methodsThe impact of exposure on GMI suppression in persistently neutropenic rabbits treated with isavuconazonium sulphate (isavuconazole-equivalent dosages of 20, 40 or 60 mg/kg every 24 h, after a 90 mg/kg loading dose) for 12 days was linked using mathematical modelling. Bridging to humans using population pharmacokinetic (PK) data from a clinical trial in invasive aspergillosis was performed using Monte Carlo simulations.
resultsMean plasma isavuconazole AUC/MIC (EC50) of 79.65 (95% CI 32.2, 127.1) produced a half-maximal effect in GMI suppression. The inhibitory sigmoid Emax curve dropped sharply after an AUC/MIC of ≥30 and was near maximum (EC80) at ∼130. Bridging the experimental PK/pharmacodynamic (PD) target to human population PK data was then used to return to the rabbit model to determine a clinically relevant PD endpoint. The clinical dosing regimen used in the trial would result in a mean GMI of 4.3 ± 1.8, which is a 50% reduction from the starting GMI in the experiment.
conclusionsThe clinical trial results showing the non-inferiority of isavuconazole to voriconazole for all-cause mortality further support the PK-PD endpoint, thereby demonstrating the usefulness of the rabbit model and endpoint for isavuconazole and implications on interpretive breakpoints. Importantly, the analysis supports this model as an important tool for development of antifungal agents.
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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.