ArticleAntimicrobial agents and chemotherapy2014
Comparative pharmacodynamics of posaconazole in neutropenic murine models of invasive pulmonary aspergillosis and mucormycosis.
Article in Antimicrobial agents and chemotherapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 50 citations in OpenAlex.
- Hypoalbuminemia and Posaconazole Therapeutic Drug Monitoring.Open forum infectious diseases · 2024Trial
- Commemorating the Landmark Advances in Our Understanding of Mucormycosis by Dimitrios P. Kontoyiannis.Journal of fungi (Basel, Switzerland) · 2025Article
- Diagnosis and management of invasive fungal infections due to non-Aspergillus moulds.The Journal of antimicrobial chemotherapy · 2025Review
- The Impact of Dimitrios P. Kontoyiannis on Mucormycosis Research.Journal of fungi (Basel, Switzerland) · 2024Article
- Rise of mucormycosis during the COVID-19 pandemic and the challenges faced.Current medical mycology · 2023Review
- Mucormycosis: A hidden mystery of fungal infection, possible diagnosis, treatment and development of new therapeutic agents.European journal of medicinal chemistry · 2023Review
- Effect of High-Dose Posaconazole on Serum Levels in Adult Patients with Hematologic Malignancy.Antimicrobial agents and chemotherapy · 2021Article
- Clinical pharmacokinetics and dose recommendations for posaconazole gastroresistant tablets in children with cystic fibrosis.The Journal of antimicrobial chemotherapy · 2021Article
- The use of posaconazole delayed-release tablets in the successful treatment of suspected mucormycosis in a bottlenose dolphin (Medical mycology case reports · 2021Article
- Dose adjustment of venetoclax when co-administered with posaconazole: clinical drug-drug interaction predictions using a PBPK approach.Cancer chemotherapy and pharmacology · 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
- Renal transplant patient survives a donor-derived abdominal invasive mucormycosis (Medical mycology case reports · 2020Article
- Antifungal Drug Repurposing.Antibiotics (Basel, Switzerland) · 2020Article
- Review
- Extrapolating Antifungal Animal Data to Humans - Is it reliable?Current fungal infection reports · 2020Article
- High-dose posaconazole for azole-resistant aspergillosis and other difficult-to-treat mould infections.Mycoses · 2020Article
- Therapeutic Challenges of Non-Antimicrobial agents and chemotherapy · 2019Review
- Animal Models to Study Mucormycosis.Journal of fungi (Basel, Switzerland) · 2019Review
- Posaconazole and isavuconazole induced hypomagnesaemia.Medical mycology case reports · 2019Article
- Endobronchial fusariosis in a child following bilateral lung transplant.Medical mycology case reports · 2019Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
Abstract
We used two established neutropenic murine models of pulmonary aspergillosis and mucormycosis to explore the association between the posaconazole area under the concentration-time curve (AUC)-to-MIC ratio (AUC/MIC) and treatment outcome. Posaconazole serum pharmacokinetics were verified in infected mice to ensure that the studied doses reflected human exposures with the oral suspension, delayed-release tablet, and intravenous formulations of posaconazole. Sinopulmonary infections were then induced in groups of neutropenic mice with Aspergillus fumigatus strain 293 (posaconazole MIC, 0.5 mg/liter) or Rhizopus oryzae strain 969 (posaconazole MIC, 2 mg/liter) and treated with escalating daily dosages of oral posaconazole, which was designed to achieve AUCs ranging from 1.10 to 392 mg · h/liter. After 5 days of treatment, lung fungal burden was analyzed by quantitative real-time PCR. The relationships of the total drug AUC/MIC and the treatment response were similar in both models, with 90% effective concentrations (EC90s) corresponding to an AUC/MIC threshold of 76 (95% confidence interval [CI], 46 to 102) for strain 293 versus 87 (95% CI, 66 to 101) for strain 969. Using a provisional AUC/MIC target of >100, these exposures correlated with minimum serum posaconazole concentrations (Cmins) of 1.25 mg/liter for strain 293 and 4.0 mg/liter for strain 969. The addition of deferasirox, but not liposomal amphotericin or caspofungin, improved the activity of a suboptimal posaconazole regimen (AUC/MIC, 33) in animals with pulmonary mucormycosis. However, no combination was as effective as the high-dose posaconazole monotherapy regimen (AUC/MIC, 184). Our analysis suggests that posaconazole pharmacodynamics are similar for A. fumigatus and R. oryzae when indexed to pathogen MICs.
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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.