Biomedical subjects

J García Rafanell

Publications and source records attributed to J García Rafanell.

10 recordsLinked to original sources

PubMed1992

In vitro and in vivo studies with flutrimazole, a new imidazole derivative with antifungal activity.

1-[(2-Fluorophenyl)(4-fluorophenyl)phenylmethyl]-1H-imidazole (flutrimazole, UR-4056, CAS 119006-77-8) is a new topical imidazole antifungal agent which displays potent broad-spectrum in vitro activity against dermatophytes, filamentous fungi and yeasts, saprophytic and pathogenic to animals and humans (MIC = 0.025-5.0 micrograms/ml). In most of these studies the activity of flutrimazole was comparable to that of clotrimazole and markedly higher than that of bifonazole (MIC differences of greater than or equal to 1 order of magnitude). Tested against Scopulariopsis brevicaulis (8 strains), both flutrimazole and clotrimazole exhibited fungistatic and fungicidal activity, and clotrimazole appeared something less active (MIC = 0.3-2.5 micrograms/ml) than flutrimazole (MIC = 0.15-0.6 micrograms/ml). In animal experiments, topical application of 1% and 2% flutrimazole, as a cream or solution, was highly effective in models of rat vaginal candidiasis and guinea-pig trichophytosis, giving a rate of cured or cured plus markedly improved animals higher than 80%. Flutrimazole shares the mode of action of other imidazole or triazole-containing antifungals, i.e. inhibition of fungal lanosterol 14 alpha-demethylase, as it strongly inhibits ergosterol biosynthesis in a cell-free homogenate of Candida albicans, with an IC50 value of 0.071 mumol/l.

Animals↗

PubMed1992

Toxicity studies with flutrimazole.

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.

Animals↗

PubMed1987

Protective effect of triflusal and acetylsalicylic acid against arachidonic acid induced cerebrovascular occlusion in anesthetized rats.

Within 60 sec after intracarotid injection of 0.33 mg/kg arachidonic acid, a pronounced attenuation of electrocortical activity, approaching electrocerebral silence, was induced in the ipsilateral hemisphere of anesthetized and heparinized rats. This effect was a consequence of the cerebrovascular occlusion due to platelet aggregates induced by arachidonic acid. This model has been used to evaluate the protective effect of acetylsalicylic acid (ASA) and of triflusal 2 hr after a single oral dose of 50 mg/kg or after 50 mg/kg, for 5 days. Pentylenetetrazol at 10 mg/kg, i.v. exerts a stimulant effect on CNS, and was used as a positive control. ASA and triflusal exhibit a protective effect in about 35% of animals when acutely administered. After chronic treatments (5 days), the effect of triflusal (60% protection) was superior to that of ASA (27% protection) (p less than 0.01).

Animals↗

PubMed1984