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Triazole-polyene antagonism in experimental invasive pulmonary aspergillosis: In vitro and in vivo correlation

  1. Author:
    Meletiadis, J.
    Petraitis, V.
    Petraitiene, R.
    Lin, P.
    Stergiopoulou, T.
    Kelaher, A. M.
    Sein, T.
    Schaufele, R. L.
    Bacher, J.
    Walsh, T. J.

  2. Author Address

    NCI, Ctr Canc Res, Pediat Oncol Branch, Immunocompromised Host Sect,NIH, Bethesda, MD 20892 USA. NIH, Surg Serv, Div Vet Resources, Off Res Serv, Bethesda, MD 20892 USA. Sci Applicat Int Corp, Frederick, MD USA.;Walsh, TJ, NCI, Ctr Canc Res, Pediat Oncol Branch, Immunocompromised Host Sect,NIH, 1-5750, Bethesda, MD 20892 USA.;walsht@mail.nih.gov
    1. Year: 2006
    2. Date: Oct
  2. Journal: Journal of Infectious Diseases
    1. 194
    2. 7
    3. Pages: 1008-1018
  4. Type of Article: Article
  5. ISSN: 0022-1899
  1. 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.

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  1. View record in Web of Science®
  2. WOS: 000240318300019

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