Interaction between posaconazole and amphotericin B in concomitant treatment against Candida albicans in vivo.
The interaction of posaconazole and amphotericin B was evaluated in concomitant treatment of Candida albicans systemic infections in immunocompetent mice by using four strains of C. albicans with different susceptibilities to fluconazole. Posaconazole and amphotericin B were each tested at four dose levels alone and in all possible combinations against each C. albicans strain. Survival curves of mice treated with combinations of posaconazole and amphotericin B were statistically compared with those of mice treated with the component monotherapies. Of the 64 total combinations evaluated against the C. albicans strains (16 combinations per strain), 20.3% were more effective in prolonging mouse survival than both of the monotherapies, 45.3% were more effective than one of the monotherapies, and 32.8% were similar to both monotherapies. No evidence of antagonism was observed between posaconazole and amphotericin B in this mouse model, consistent with in vitro results against the same strains.
Cacciapuoti
Anthony
A
Schering-Plough Research Institute, 2015 Galloping Hill Rd., Kenilworth, NJ 07033, USA. anthony.cacciapuoti@spcorp.com
Gurnani
Maya
M
Halpern
Judith
J
Norris
Christine
C
Patel
Reena
R
Loebenberg
David
D
D000666:Amphotericin B / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002176:Candida albicans / Q000187:drug effects*; D002177:Candidiasis / Q000188:drug therapy* / Q000382:microbiology / Q000401:mortality; D004347:Drug Interactions; D008297:Male; D051379:Mice; D016019:Survival Analysis; D014230:Triazoles / Q000494:pharmacology* / Q000627:therapeutic use
D000935:Antifungal Agents; D014230:Triazoles; C101425:posaconazole; D000666:Amphotericin B