ArticleAntimicrobial agents and chemotherapy2011
Posaconazole in human serum: a greater pharmacodynamic effect than predicted by the non-protein-bound serum concentration.
Article in Antimicrobial agents and chemotherapy, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 32 citations in OpenAlex.
- Practice Guidelines for the Diagnosis and Management of Aspergillosis: 2016 Update by the Infectious Diseases Society of America.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2016Guideline
- Hypoalbuminemia and Posaconazole Therapeutic Drug Monitoring.Open forum infectious diseases · 2024Trial
- Evaluation of anAntimicrobial agents and chemotherapy · 2026Article
- Whole Body Physiologically Based Pharmacokinetic Model to Explain A Patient With Drug-Drug Interaction Between Voriconazole and Flucloxacillin.European journal of drug metabolism and pharmacokinetics · 2024Article
- An Update on Breakthrough Invasive Mold Infections.Mycopathologia · 2024Review
- Relative Performance of Volume of Distribution Prediction Methods for Lipophilic Drugs with Uncertainty in LogP Value.Pharmaceutical research · 2024Article
- Real-world Experience of Posaconazole Therapeutic Drug Monitoring in Oncology Patients: Clinical Implications of Hypoalbuminemia as a Predictor of Subtherapeutic Posaconazole Levels.Open forum infectious diseases · 2024Article
- Dosing Optimization of Posaconazole in Lung-Transplant Recipients Based on Population Pharmacokinetic Model.Antibiotics (Basel, Switzerland) · 2023Article
- Development of an in vitro pharmacokinetic/pharmacodynamic model in the presence of serum for studying micafungin activity against Candida albicans: a need for revision of CLSI susceptibility breakpoints.The Journal of antimicrobial chemotherapy · 2023Article
- Advancing posaconazole quantification analysis with a new reverse-phase HPLC method in its bulk and marketed dosage form.F1000Research · 2023Article
- The Role of New Posaconazole Formulations in the Treatment of Candida albicans Infections: Data from anAntimicrobial agents and chemotherapy · 2021Article
- Population pharmacokinetics of total and unbound concentrations of intravenous posaconazole in adult critically ill patients.Critical care (London, England) · 2019Observational
- 4-Aminopyridyl-based CYP51 inhibitors as anti-Trypanosoma cruzi drug leads with improved pharmacokinetic profile and in vivo potency.Journal of medicinal chemistry · 2014Article
- Posaconazole concentrations in human tissues after allogeneic stem cell transplantation.Antimicrobial agents and chemotherapy · 2014Article
- Understanding antifungal prophylaxis with posaconazole in hematology patients: an evolving bedside to bench story.Haematologica · 2014Article
- Tissue penetration of antifungal agents.Clinical microbiology reviews · 2014Review
- Terbinafine in combination with other antifungal agents for treatment of resistant or refractory mycoses: investigating optimal dosing regimens using a physiologically based pharmacokinetic model.Antimicrobial agents and chemotherapy · 2014Article
- Pharmacokinetics of posaconazole within epithelial cells and fungi: insights into potential mechanisms of action during treatment and prophylaxis.The Journal of infectious diseases · 2013Article
- Inhibitory and fungicidal effects of antifungal drugs against Aspergillus species in the presence of serum.Antimicrobial agents and chemotherapy · 2013Article
- Posaconazole exposure-response relationship: evaluating the utility of therapeutic drug monitoring.Antimicrobial agents and chemotherapy · 2012Review
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
It is generally accepted that only the unbound fraction of a drug is pharmacologically active. Posaconazole is an antifungal agent with a protein binding of 98 to 99%. Taking into account the degree of protein binding, plasma levels in patients, and MIC levels of susceptible strains, it can be assumed that the free concentration of posaconazole sometimes will be too low to exert the expected antifungal effect. The aim was therefore to test the activity of posaconazole in serum in comparison with that of the calculated unbound concentrations in protein-free media. Significant differences (P < 0.05) from the serum control were found at serum concentrations of posaconazole of 1.0 and 0.10 mg/liter, with calculated free concentrations corresponding to 1× MIC and 0.1× MIC, respectively, against one Candida lusitaniae strain selected for proof of principle. In RPMI 1640, the corresponding calculated unbound concentration of 0.015 mg/liter resulted in a significant effect, whereas that of 0.0015 mg/liter did not. Also, against seven additional Candida strains tested, there was an effect of the low posaconazole concentration in serum, in contrast to the results in RPMI 1640. Fluconazole, a low-grade-protein-bound antifungal, was used for comparison at corresponding concentrations in serum and RPMI 1640. No effect was observed at the serum concentration, resulting in a calculated unbound concentration of 0.1× MIC. In summary, there was a substantially greater pharmacodynamic effect of posaconazole in human serum than could be predicted by the non-protein-bound serum concentration. A flux from serum protein-bound to fungal lanosterol 14α-demethylase-bound posaconazole is suggested.
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Registered trials
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