Evidence map›Paper›PMID 20439615›Full record

ArticleAntimicrobial agents and chemotherapy2010

Pharmacokinetics and pharmacodynamics of amphotericin B deoxycholate, liposomal amphotericin B, and amphotericin B lipid complex in an in vitro model of invasive pulmonary aspergillosis.

Jodi M Lestner, Susan J Howard, Joanne Goodwin, Lea Gregson, Jayesh Majithiya, Thomas J Walsh, Gerard M Jensen, William W Hope

Open access · greenAbstract read
In one paragraph

Article in Antimicrobial agents and chemotherapy, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed, 1 pooled it
2.1field-weighted citation impact, top 13% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

33 citing papers in PubMed, 1 synthesis or guideline pooled it, 53 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Recent innovations and challenges in the treatment of fungal infections.Frontiers in cellular and infection microbiology · 2025
    Review
  4. Antimicrobial agents and chemotherapy · 2024
    Article
  5. Article
  6. Review
  7. Review
  8. Review
  9. Article
  10. Review
  11. Article
  12. Antifungal Drugs Influence Neutrophil Effector Functions.Antimicrobial agents and chemotherapy · 2019
    Article
  13. Antimicrobial agents and chemotherapy · 2019
    Article
  14. Article
  15. Clinical Pharmacokinetics, Pharmacodynamics, Safety and Efficacy of Liposomal Amphotericin B.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2019
    Review
  16. Article
  17. Article
  18. Comparative efficacy, toxicity and biodistribution of the liposomal amphotericin B formulations FungisomeInternational journal for parasitology. Drugs and drug resistance · 2018
    Article
  19. Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 4 institutions in 2 countries.

Jodi M LestnerThe University of Manchester, Manchester Academic Health Science Centre, NIHR Translational Research Facility in Respiratory Medicine, University Hospital of South Manchester NHS Foundation Trust, 1.800 Stopford Building, Oxford Road, Manchester M13 9PT, United Kingdom.
Susan J Howard
Joanne Goodwin
Lea Gregson
Jayesh Majithiya
Thomas J Walsh
Gerard M Jensen
William W Hope
Manchester Academic Health Science Centre · GBUniversity of Manchester · GBGilead Sciences (United States) · USNational Cancer Institute · US

Funding

Department of HealthNational Centre for the Replacement, Refinement and Reduction of Animals in Research G0700599/1
6 · The paper itself

Abstract

The pharmacodynamic and pharmacokinetic (PK-PD) properties of amphotericin B (AmB) formulations against invasive pulmonary aspergillosis (IPA) are not well understood. We used an in vitro model of IPA to further elucidate the PK-PD of amphotericin B deoxycholate (DAmB), liposomal amphotericin B (LAmB) and amphotericin B lipid complex (ABLC). The pharmacokinetics of these formulations for endovascular fluid, endothelial cells, and alveolar cells were estimated. Pharmacodynamic relationships were defined by measuring concentrations of galactomannan in endovascular and alveolar compartments. Confocal microscopy was used to visualize fungal biomass. A mathematical model was used to calculate the area under the concentration-time curve (AUC) in each compartment and estimate the extent of drug penetration. The interaction of LAmB with host cells and hyphae was visualized using sulforhodamine B-labeled liposomes. The MICs for the pure compound and the three formulations were comparable (0.125 to 0.25 mg/liter). For all formulations, concentrations of AmB progressively declined in the endovascular fluid as the drug distributed into the cellular bilayer. Depending on the formulation, the AUCs for AmB were 10 to 300 times higher within the cells than within endovascular fluid. The concentrations producing a 50% maximal effect (EC50) in the endovascular compartment were 0.12, 1.03, and 4.41 mg/liter for DAmB, LAmB, and ABLC, respectively, whereas, the EC50 in the alveolar compartment were 0.17, 7.76, and 39.34 mg/liter, respectively. Confocal microscopy suggested that liposomes interacted directly with hyphae and host cells. The PK-PD relationships of the three most widely used formulations of AmB differ markedly within an in vitro lung model of IPA.

Indexed as

Antifungal AgentsModels, BiologicalAmphotericin BArea Under CurveCell LineDeoxycholic AcidDrug CombinationsEndothelial CellsEpithelial CellsHumansInvasive Pulmonary AspergillosisLung Diseases, FungalMicrobial Sensitivity TestsPulmonary AlveoliAmphotericin Bamphotericin B, deoxycholate drug combinationAntifungal AgentsDeoxycholic AcidDrug Combinationsliposomal amphotericin B

Identifiers

PMID20439615
PMCPMC2916353
OpenAlexW2089384079

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.