In vivo fungicidal effect of KP-103 in a guinea pig model of interdigital tinea pedis determined by using a new method for removing the antimycotic carryover effect.
We developed a new technique for culture study that successfully recovers fungi from drug-treated skin tissues, in which tissue specimens were homogenized, dialyzed against water, digested with trypsin, and then washed with PBS, to eliminate the drug that remaining in the skin tissue specimens. With this modified culture method, we reevaluated the efficacy of KP-103, neticonazole, and lanoconazole in a guinea pig interdigital tinea pedis model. Guinea pigs with tinea pedis were topically treated with a 1% solution of KP-103 or a reference drug once a day for 10 consecutive days. Five days after the last treatment, left and right feet were subjected to culture study by the conventional and modified recovery culture methods, respectively. One hundred percent (20/20) of lanoconazole-treated feet were judged as culture-negative by the conventional culture method, but 85% (17/20) of the feet were shown to be culture-positive when the modified recovery culture method was used. On the other hand, KP-103 achieved high rates of culture-negative rates, 95% (19/20) and 85% (17/20), in both conventional and modified culture methods, respectively. Furthermore, on day-30 posttreatment, KP-103 sterilized 14 of the 20 infected feet, whereas neticonazole and lanoconazole were not effective even in reducing fungal burden. KP-103 proved to be highly effective in achieving mycological cure and preventing relapse against tinea pedis presumably because of its good bioavailability in the skin based on its low keratin-affinity, along with its potent antifungal activity.
Tatsumi
Yoshiyuki
Y
Central Research Laboratories, Kaken Pharmaceutical Co., Ltd., Kyoto, Japan. tatsumi_yoshiyuki@kaken.co.jp
Yokoo
Mamoru
M
Arika
Tadashi
T
Yamaguchi
Hideyo
H
D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D015169:Colony Count, Microbial; D003470:Culture Media; D004353:Drug Evaluation, Preclinical; D006168:Guinea Pigs; D006571:Heterocyclic Compounds / Q000493:pharmacokinetics; D007093:Imidazoles / Q000493:pharmacokinetics; D008297:Male; D008826:Microbial Sensitivity Tests / Q000379:methods*; D023421:Models, Animal; D013997:Time Factors; D014008:Tinea Pedis / Q000188:drug therapy* / Q000473:pathology; D016896:Treatment Outcome; D014230:Triazoles / Q000008:administration & dosage / Q000627:therapeutic use*; D014249:Trichophyton / Q000187:drug effects / Q000254:growth & development / Q000472:pathogenicity
D000935:Antifungal Agents; D003470:Culture Media; D006571:Heterocyclic Compounds; D007093:Imidazoles; D014230:Triazoles; C072774:latoconazole; C431707:efinaconazole; C084784:neticonazole