TY - JOUR
T1 - Triazole-polyene antagonism in experimental invasive pulmonary aspergillosis
T2 - In vitro and in vivo correlation
AU - Meletiadis, Joseph
AU - Petraitis, Vidmantas
AU - Petraitiene, Ruta
AU - Lin, Pengxin
AU - Stergiopoulou, Theodouli
AU - Kelaher, Amy M.
AU - Sein, Tin
AU - Schaufele, Robert L.
AU - Bacher, John
AU - Walsh, Thomas J.
N1 - Funding Information:
Received 27 December 2005; accepted 18 April 2006; electronically published 28 August 2006. Potential conflicts of interest: none reported. Financial support: Intramural Research Program of the National Institutes of Health and the National Cancer Institute. Reprints or correspondence: Dr. Thomas J. Walsh, 10 Center Dr., Center for Cancer Research, 1-5750, National Cancer Institute, Pediatric Oncology Branch, Bethesda, MD 20892 (walsht@mail.nih.gov).
PY - 2006/10/1
Y1 - 2006/10/1
N2 - 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.
AB - 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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U2 - 10.1086/506617
DO - 10.1086/506617
M3 - Article
C2 - 16960790
AN - SCOPUS:33748994832
VL - 194
SP - 1008
EP - 1018
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
SN - 0022-1899
IS - 7
ER -