Triazole-polyene antagonism in experimental invasive pulmonary aspergillosis: in vitro and in vivo correlation. Academic Article uri icon

Overview

MeSH

  • Animals
  • Drug Antagonism
  • Drug Therapy, Combination
  • Humans
  • Microbial Sensitivity Tests
  • Models, Biological
  • Polyenes
  • Rabbits

MeSH Major

  • Amphotericin B
  • Antifungal Agents
  • Aspergillosis
  • Aspergillus fumigatus
  • Liposomes
  • Lung Diseases, Fungal
  • Thiazoles
  • Triazoles

abstract

  • Combination antifungal therapy is increasingly used in the treatment of invasive aspergillosis. Whether the interaction between amphotericin B and triazoles is antagonistic against invasive aspergillosis is a controversial issue that is not likely to be resolved through a randomized clinical trial. Here, we found both in vitro and in vivo antagonism between liposomal amphotericin B and ravuconazole in simultaneous treatment of experimental invasive pulmonary aspergillosis in persistently neutropenic rabbits. Bliss independence-based drug-interaction modeling showed significant antagonism in vitro and in vivo, with the observed drug effects being 20%-69% lower than would be expected if the drugs were acting independently. These in vitro and in vivo findings of antagonism were consistent with the findings from Loewe additivity-based drug-interaction modeling. No pharmacokinetic interaction was found. The combination of a triazole and polyene may be antagonistic in the treatment of invasive pulmonary aspergillosis.

publication date

  • October 1, 2006

has subject area

  • Amphotericin B
  • Animals
  • Antifungal Agents
  • Aspergillosis
  • Aspergillus fumigatus
  • Drug Antagonism
  • Drug Therapy, Combination
  • Humans
  • Liposomes
  • Lung Diseases, Fungal
  • Microbial Sensitivity Tests
  • Models, Biological
  • Polyenes
  • Rabbits
  • Thiazoles
  • Triazoles

Research

keywords

  • Journal Article

Identity

Language

  • eng

Digital Object Identifier (DOI)

  • 10.1086/506617

PubMed ID

  • 16960790

Additional Document Info

start page

  • 1008

end page

  • 1018

volume

  • 194

number

  • 7