Vericat M L, García Rafanell J, Forn J, Casadesús A, Alumá J, Zapatero J
Research Center, J. Uriach & Cía, S.A., Barcelona, Spain.
Arzneimittelforschung. 1992 Jun;42(6):841-6.
Studies with 1-[(2-fluorophenyl)(4-fluorophenyl)phenylmethyl]-1H- imidazole (flutrimazole, CAS 119006-77-8), a new topical imidazole antifungal agent, have been carried out to investigate the acute toxicity of the active substance in mice and rats, as well as the acute ocular and dermal irritation in rabbits, the dermal tolerance after repeated dose (21 days) applications in rabbits, and the sensitising, photoallergic and phototoxic potential in guinea pigs using 1% flutrimazole cream. LD50 values after oral or intraperitoneal administration were greater than or equal to 1000 mg/kg in both mice and rats, which reveal a very low acute toxicity of flutrimazole. No differences were found between the excipient and 1% flutrimazole cream in the acute ocular and dermal irritation studies in rabbits, the irritation indexes being indicative of no lesions due to flutrimazole. Cumulative dermal irritation studies in rabbits showed an improved local tolerance of a skin cream containing 1% flutrimazole as compared to a commercial skin cream containing 1% clotrimazole. The irritation indexes were 1.2 and 3.7, respectively (p less than 0.01). The corresponding histophatological findings confirmed the better local tolerance of 1% flutrimazole cream. Furthermore, it has been found that flutrimazole cream lacks sensitising potential (Magnusson and Kligman test), is also devoid of phototoxic potential and does not induce photoallergic reactions in guinea pigs, these data being confirmed by histopathological studies. These results, together with the very slight systemic absorption rate of flutrimazole from the 1% topical drug form, clearly show that no restrictions should be taken in the use of the cream for reasons of systemic toxicity or dermal tolerance.
对新型局部用咪唑类抗真菌药1-[(2-氟苯基)(4-氟苯基)苯甲基]-1H-咪唑（氟曲马唑，CAS 119006-77-8）进行了多项研究，以考察该活性物质对小鼠和大鼠的急性毒性、对家兔的急性眼刺激性和皮肤刺激性、在家兔身上重复给药（21天）后的皮肤耐受性，以及使用1%氟曲马唑乳膏对豚鼠的致敏、光变态反应和光毒性潜力。小鼠和大鼠经口或腹腔给药后的半数致死量值均大于或等于1000 mg/kg，这表明氟曲马唑的急性毒性非常低。在家兔急性眼刺激性和皮肤刺激性研究中，赋形剂与1%氟曲马唑乳膏之间未发现差异，刺激指数表明氟曲马唑未造成损伤。家兔累积皮肤刺激性研究表明，与含1%克霉唑的市售皮肤乳膏相比，含1%氟曲马唑的皮肤乳膏局部耐受性有所改善。刺激指数分别为1.2和3.7（p<0.01）。相应的组织病理学结果证实了1%氟曲马唑乳膏具有更好的局部耐受性。此外，还发现氟曲马唑乳膏缺乏致敏潜力（Magnusson和Kligman试验），也没有光毒性潜力，并且不会在豚鼠中诱发光变态反应，这些数据得到了组织病理学研究的证实。这些结果，连同氟曲马唑从1%局部用药剂型的全身吸收率非常低，清楚地表明，不应因全身毒性或皮肤耐受性原因而对该乳膏的使用加以限制。
