ArticleAntimicrobial agents and chemotherapy2006
Pharmacodynamic activity of amphotericin B deoxycholate is associated with peak plasma concentrations in a neutropenic murine model of invasive pulmonary aspergillosis.
Article in Antimicrobial agents and chemotherapy, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 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.
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
38 citing papers in PubMed, 1 synthesis or guideline pooled it, 102 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
- Fixed Dosing of Liposomal Amphotericin B in Morbidly Obese Individuals.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2020Trial
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- Inhaled Antifungal Agents for Treatment and Prophylaxis of Bronchopulmonary Invasive Mold Infections.Pharmaceutics · 2022Review
- Role and Interpretation of Antifungal Susceptibility Testing for the Management of Invasive Fungal Infections.Journal of fungi (Basel, Switzerland) · 2020Review
- Systemic and Target-Site Pharmacokinetics of Antiparasitic Agents.Clinical pharmacokinetics · 2020Review
- Administration and Dosing of Systemic Antifungal Agents in Pediatric Patients.Paediatric drugs · 2020Review
- Extrapolating Antifungal Animal Data to Humans - Is it reliable?Current fungal infection reports · 2020Article
- Minimum concentration of Amphotericin B in serum according to the formulation, dose, and daily or prolonged intermittent therapeutic regimen.Revista da Sociedade Brasileira de Medicina Tropical · 2020Article
- Extended Dosing Regimens for Fungal Prophylaxis.Clinical microbiology reviews · 2019Review
- Preclinical Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Antifungal Activity of Liposomal Amphotericin B.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2019Review
- Clinical Pharmacokinetics, Pharmacodynamics, Safety and Efficacy of Liposomal Amphotericin B.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2019Review
- Pharmacology of Liposomal Amphotericin B: An Introduction to Preclinical and Clinical Advances for Treatment of Life-threatening Invasive Fungal Infections.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2019Article
- Surveillance for azoles resistance in Aspergillus spp. highlights a high number of amphotericin B-resistant isolates.Mycoses · 2018Article
- Pharmacokinetics of antifungal drugs: practical implications for optimized treatment of patients.Infection · 2017Review
- Optimization of polyene-azole combination therapy against aspergillosis using an in vitro pharmacokinetic-pharmacodynamic model.Antimicrobial agents and chemotherapy · 2015Article
- Pharmacodynamics of amphotericin B deoxycholate, amphotericin B lipid complex, and liposomal amphotericin B against Aspergillus fumigatus.Antimicrobial agents and chemotherapy · 2015Article
- Antifungal pharmacokinetics and pharmacodynamics.Cold Spring Harbor perspectives in medicine · 2014Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
We conducted a dose fractionation study of neutropenic, corticosteroid-immunosuppressed mice to characterize the pharmacodynamic/pharmacokinetic (PK/PD) parameter most closely associated with amphotericin B (AMB) efficacy in the treatment of invasive pulmonary aspergillosis. Pharmacokinetic parameter estimates were determined by a nonparametric population pharmacokinetic analysis of plasma drug concentrations following single intraperitoneal doses (0.25, 1.0, and 3.0 mg/kg of body weight) of amphotericin B deoxycholate. Three dosage groups (0.5, 0.75, and 1.0 mg/kg) fractionated into three dosing intervals (every 8 h [q8h], q24h, or q72h) were tested to discriminate between the PK/PD parameters (the ratio of maximum concentration of drug in serum [Cmax]/MIC, the ratio of area under the concentration-time curve/MIC, and percentage of time above MIC) most closely associated with AMB efficacy over a range of clinically achievable exposures in humans. The efficacy of each regimen was determined by quantitative PCR and survival. Reductions in pulmonary fungal burden and improvements in survival were maximized at the highest peak plasma concentrations in each of the dosage groups. Reductions in pulmonary fungal burden and increased survival were most closely associated with Cmax/MIC, with maximal activity occurring as the Cmax/MIC approached 2.4. In our model, Cmax/MIC is the PK/PD parameter most closely associated with efficacy in the treatment of invasive pulmonary aspergillosis. These data predict that less frequently administered, higher dosages of AMB would optimize efficacy.
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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.