Triazole-polyene antagonism in experimental invasive pulmonary aspergillosis: in vitro and in vivo correlation.
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.
Meletiadis
Joseph
J
Immunocompromised Host Section, Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA.
Petraitis
Vidmantas
V
Petraitiene
Ruta
R
Lin
Pengxin
P
Stergiopoulou
Theodouli
T
Kelaher
Amy M
AM
Sein
Tin
T
Schaufele
Robert L
RL
Bacher
John
J
Walsh
Thomas J
TJ
D000666:Amphotericin B / Q000037:antagonists & inhibitors* / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000935:Antifungal Agents / Q000037:antagonists & inhibitors* / Q000494:pharmacology / Q000627:therapeutic use; D001228:Aspergillosis / Q000188:drug therapy*; D001232:Aspergillus fumigatus / Q000187:drug effects*; D004336:Drug Antagonism; D004359:Drug Therapy, Combination; D006801:Humans; D008081:Liposomes / Q000037:antagonists & inhibitors* / Q000494:pharmacology / Q000627:therapeutic use; D008172:Lung Diseases, Fungal / Q000188:drug therapy*; D008826:Microbial Sensitivity Tests; D008954:Models, Biological; D011090:Polyenes / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D011817:Rabbits; D013844:Thiazoles / Q000037:antagonists & inhibitors* / Q000494:pharmacology / Q000627:therapeutic use; D014230:Triazoles / Q000037:antagonists & inhibitors* / Q000494:pharmacology / Q000627:therapeutic use
D000935:Antifungal Agents; D008081:Liposomes; D011090:Polyenes; D013844:Thiazoles; D014230:Triazoles; C068538:liposomal amphotericin B; D000666:Amphotericin B; C104066:ER 30346