ArticleAntimicrobial agents and chemotherapy2009
Pharmacokinetics and pharmacodynamics of a novel triazole, isavuconazole: mathematical modeling, importance of tissue concentrations, and impact of immune status on antifungal effect.
Article in Antimicrobial agents and chemotherapy, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers, 1 of them a synthesis that pooled it.
What it found
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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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
43 citing papers in PubMed, 1 synthesis or guideline pooled it, 86 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
- A phase 2, randomized, double-blind, multicenter trial to evaluate the safety and efficacy of three dosing regimens of isavuconazole compared with fluconazole in patients with uncomplicated esophageal candidiasis.Antimicrobial agents and chemotherapy · 2015Trial
- Ibrexafungerp is efficacious in a neutropenic murine model of pulmonary mucormycosis as monotherapy and combined with liposomal amphotericin B.Antimicrobial agents and chemotherapy · 2024Article
- Recommendations on the use of azole antifungals in hematology-oncology patients.Revista espanola de quimioterapia : publicacion oficial de la Sociedad Espanola de Quimioterapia · 2023Review
- A Hybrid Algorithm Combining Population Pharmacokinetic and Machine Learning for Isavuconazole Exposure Prediction.Pharmaceutical research · 2023Article
- Postantifungal Effect of Antifungal Drugs againstJournal of fungi (Basel, Switzerland) · 2022Review
- The Overview on the Pharmacokinetic and Pharmacodynamic Interactions of Triazoles.Pharmaceutics · 2021Review
- Model-Informed Drug Development for Anti-Infectives: State of the Art and Future.Clinical pharmacology and therapeutics · 2021Review
- In Vitro Synergistic Interactions of Isavuconazole and Echinocandins againstAntibiotics (Basel, Switzerland) · 2021Article
- Population Pharmacokinetics of Intravenous Isavuconazole in Solid-Organ Transplant Recipients.Antimicrobial agents and chemotherapy · 2020Article
- Click Chemistry in the Design and Production of Hybrid Tracers.ACS omega · 2019Article
- Tissue Distribution and Penetration of Isavuconazole at the Site of Infection in Experimental Invasive Aspergillosis in Mice with Underlying Chronic Granulomatous Disease.Antimicrobial agents and chemotherapy · 2019Article
- CYP51 as drug targets for fungi and protozoan parasites: past, present and future.Parasitology · 2018Review
- Clinical Pharmacokinetics and Pharmacodynamics of Isavuconazole.Clinical pharmacokinetics · 2018Review
- Review
- Isavuconazole Is Effective for the Treatment of Experimental Cryptococcal Meningitis.Antimicrobial agents and chemotherapy · 2016Article
- Isavuconazole Population Pharmacokinetic Analysis Using Nonparametric Estimation in Patients with Invasive Fungal Disease (Results from the VITAL Study).Antimicrobial agents and chemotherapy · 2016Article
- Isavuconazole for the treatment of invasive aspergillosis and mucormycosis: current evidence, safety, efficacy, and clinical recommendations.Infection and drug resistance · 2016Review
- Isavuconazole in the treatment of invasive aspergillosis and mucormycosis infections.Infection and drug resistance · 2016Review
- Role of isavuconazole in the treatment of invasive fungal infections.Therapeutics and clinical risk management · 2016Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Isavuconazole is a triazole with broad-spectrum activity against medically important fungal pathogens. We investigated the pharmacokinetics and pharmacodynamics of isavuconazole in a murine model of disseminated candidiasis. We determined the pharmacokinetics in both plasma and kidney. The relationship between tissue concentrations and the resultant antifungal effect was described using a mathematical model. The pharmacodynamic parameter that optimally links drug exposure with the antifungal effect was determined using dose fractionation studies. The impact of the immune status of mice receiving isavuconazole was determined in persistently and temporarily neutropenic animals. The pharmacokinetics of 1.6 to 28 mg isavuconazole/kg of body weight were linear. Exposure-response relationships demonstrated near-maximal effect following the administration of >15 mg/kg. The mathematical model showed that exposures in the kidney were 5.77 times higher than those in plasma, and there was persistence of the drug at this site despite concentrations in plasma falling to undetectable levels. The in vitro and in vivo postantifungal effects were 2 to 5 and 8.41 h, respectively. The area under the concentration-time curve (AUC)/MIC ratio was the parameter that optimally linked drug exposure with the observed antifungal effect. The total drug AUC/MIC ratios associated with a 90% probability of survival in temporarily and persistently neutropenic mice were 270 and 670, respectively. Once corrected for protein binding, these values are similar to the magnitude of drug exposure associated with a high probability of a successful therapeutic outcome for other triazoles. This study provides the experimental foundation for the use of isavuconazole in patients with disseminated candidiasis.
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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.