In vitro and in vivo activities of the novel azole antifungal agent r126638.
R126638 is a new triazole agent with potent antifungal activity in vitro against various dermatophytes, Candida spp., and Malassezia spp. Its activity against Malassezia spp. in vitro was superior to that of ketoconazole, the agent currently used for the treatment of Malassezia-related infections. R126638 showed activity comparable to or lower than that of itraconazole against dermatophytes in vitro; however, in guinea pig models of dermatophyte infections, R126638 given orally consistently showed antifungal activity superior to that of itraconazole, with 50% effective doses (ED(50)s) three- to more than eightfold lower than those of itraconazole, depending on the time of initiation and the duration of treatment. The ED(50) of R126638 in a mouse dermatophytosis model was more than fivefold lower than that of itraconazole. These data indicate that if the effects of R126638 seen when it is used to treat animals can be extrapolated to humans, the novel compound would be expected to show effects at doses lower than those of existing drugs and, hence, present a lower risk for side effects.
Odds
F
F
University of Aberdeen, Aberdeen, United Kingdom.
Ausma
J
J
Van Gerven
F
F
Woestenborghs
F
F
Meerpoel
L
L
Heeres
J
J
Vanden Bossche
H
H
Borgers
M
M
D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D002175:Candida / Q000187:drug effects; D003881:Dermatomycoses / Q000188:drug therapy* / Q000382:microbiology; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D007093:Imidazoles / Q000138:chemical synthesis* / Q000627:therapeutic use*; D017964:Itraconazole / Q000494:pharmacology / Q000627:therapeutic use; D007654:Ketoconazole / Q000494:pharmacology / Q000627:therapeutic use; D051379:Mice; D008826:Microbial Sensitivity Tests; D016814:Microsporidia / Q000187:drug effects*; D012867:Skin / Q000382:microbiology; D014005:Tinea / Q000188:drug therapy* / Q000382:microbiology; D014230:Triazoles / Q000138:chemical synthesis* / Q000627:therapeutic use*; D014249:Trichophyton / Q000187:drug effects*
D000935:Antifungal Agents; D007093:Imidazoles; D014230:Triazoles; D017964:Itraconazole; C482452:pramiconazole; D007654:Ketoconazole