In vivo efficacy of SM-8668 (Sch 39304), a new oral triazole antifungal agent.
SM-8668 (Sch 39304) is a new oral antifungal agent which we evaluated in comparison with fluconazole in various fungal infection models. The prophylactic effect of SM-8668 was excellent against systemic candidiasis, aspergillosis, and cryptococcosis in mice. The 50% effective dose for SM-8668 was assessed at 10 days after infection and was 0.18, 3.7, and 5.9 mg/kg (body weight), respectively, for the above-mentioned fungal diseases. Fluconazole was about four times less effective than SM-8668 against systemic candidiasis and was only slightly effective at doses of 80 and 25 mg/kg against systemic aspergilosis and cryptococcosis, respectively. SM-8668 was also about four to eight times more active than fluconazole against vaginal candidiasis in rats and against dermatophytic infection in guinea pigs. In addition, topical SM-8668 was as effective as topical miconazole or tioconazole against skin mycosis in guinea pigs. After oral administration, SM-8668 showed a maximum concentration in serum similar to that of fluconazole in both mice and rats, but the elimination half-life and area under the serum concentration-time curve for SM-8668 were twice those for fluconazole.
Research Laboratories, Sumitomo Pharmaceuticals Co., Ltd., Osaka, Japan.
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Tanio
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Ichise
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Nakajima
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Okuda
D000279:Administration, Cutaneous; D000284:Administration, Oral; D000818:Animals; D000935:Antifungal Agents / Q000097:blood / Q000627:therapeutic use*; D001228:Aspergillosis / Q000188:drug therapy; D001232:Aspergillus fumigatus / Q000187:drug effects; D002181:Candidiasis, Vulvovaginal / Q000188:drug therapy; D003453:Cryptococcosis / Q000188:drug therapy; D005260:Female; D015725:Fluconazole / Q000097:blood / Q000627:therapeutic use; D006168:Guinea Pigs; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D051381:Rats; D011919:Rats, Inbred Strains; D014005:Tinea / Q000188:drug therapy; D014230:Triazoles / Q000097:blood / Q000627:therapeutic use*
D000935:Antifungal Agents; D014230:Triazoles; C056513:Sch 39304; D015725:Fluconazole