The efficacy of orally applied terbinafine, itraconazole and fluconazole in models of experimental trichophytoses

The antimycotic efficacy of terbinafine, itraconazole and fluconazole was evaluated in guinea-pig trichophytoses (Trichophyton mentagrophytes, Trichophyton rubrum) by use of the hair root invasion test (HIT) and the auricular skin temperature test (STT). In the prophylactic HIT model using T. mentagrophytes as the infective agent, statistical evaluation of the ratios of protected/inoculated animals revealed ED50 values of 2.8 mg kg-1 for terbinafine, 10.7 mg kg-1 for itraconazole and 11.6 mg kg-1 for fluconazole. When T. rubrum was used in the same model the ED50 value of terbinafine was 7.3 mg kg-1 whereas only two of eight animals became protected by itraconazole and fluconazole at the highest dose of 16 mg kg-1. In the therapeutic HIT model carried out with T. mentagrophytes, the curative doses were increased for all test compounds, revealing an ED50 of 12.3 mg kg-1 for terbinafine and > 40 mg kg-1 for itraconazole and fluconazole. In the STT model, decline of temperature was quicker and more pronounced during therapy with terbinafine than during treatment with the triazole derivatives. Skin temperature was back to normal on day 8 (after seven treatments) with 20 mg kg-1 terbinafine, whereas a decline to, or almost to, physiological skin temperature was not observed until day 24 (5 days after the last treatment) in animals treated with 40 mg kg-1 itraconazole or fluconazole.