In vitro and in vivo activity and local tolerance of a new antifungal agent. Comparison with bifonazole (in vitro) and cotrimazole (in vitro and in vivo)

In vitro and in vivo activity and local tolerance of a new antifungal agent. Comparison with bifonazole (in vitro) and cotrimazole (in vitro and in vivo)

1201 I P.we.031 I In vitro and in vivo activity and local tolerance of a new antifungal agent. Comparison with bifonazole (in vitro) and cotrimazole ...

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1201 I P.we.031 I

In vitro and in vivo activity and local tolerance of a new antifungal agent. Comparison with bifonazole (in vitro) and cotrimazole (in vitro and in vivo) Garcia-Rafanell, J,, Alguer6, M., Vericat, M,L., Fore, J., Torres *, J.M., Basi * *, N. and Zapatero * * , J. Research Center, J. Uriach and C|a. S.A., Deg~ Bal;~ 59, G~,026Barcelona, * Dept. of Clinical Microbiology, Ho,pital dei Mar, Passeig Maritim 25, 08002 Barcelona and * * Centro de Investigaci6n y Desarrolio Aplicado, S.A.L., Argenters 6, 08130 Sta. Perpetua de Mogoda, Barcelona, Spain

1-[(2-fluorophenyl)(4ofluorophenyl)phenylmethyl]-lH-imidazole (UR-4056) is a new topical imidazole antifungal agent which disp!ays potent broadspectrum in vitro activity against dermatophytes, filamentous fungi and yeasts, giving minimum inhibitory concentration (MIC) values ranging from 0.025 to 5.0 pg/m.l. Clinical isolates of Candida albicans (C.A.) and C. tropicalis were moderately sensitive, most strains being inhibited at a concentration of 2.5 or 5.0 pg/ml. Clinical isolates of Trichophyton mentagrophytes (T.M.) were more sensitive, most MIC values for UR-4056 being 0.6 pg/ml. Against Scopulariopsis bravicaulis (8 strains), UR-4056 ga,;e MIC values ranging from 0.15 to 0.6 v~g/ml (clotrimazole: 0.3 to 2.5 pg/ml). The majority of MIC values for bifonazole were markedly higher ( > 1 order of magnitude) than those of UR-4056 or clotrimazole (CL). In in vivo tests, topical UR-4056 (2% w / v in polyethylene glycol 400, 100 pl, 3 b.i.d.) gave a cure rate of 68% (15/22) and 82% (18/22), 3 and 7 days after the !ast administration, respectively, against vaginal candidosis induced by C.A. in rats. CL, in the same experim~ntal conditions, showed 587o (15/26) and 35% (9/26) cure rate. Spontaneous cure rate in controls was 10% (3/29) (p < 0.05 versus CL, and p < 0.01 versus UR-4056) and 247o (7/29) (p < 0.01 versus UR 4056). In an in vivo model of dermatophytosis due to T.M., strain MR-TR120, in guinea pigs, both URo4056 and CL displayed similar effectiveness, giving a rate of cured + markedly improved animals of 877o (13/15) against 40~ (8/20) of controls, after 10 days topical applications (2 weeks) of skin creams containing 1% w / w of active ingredient. A 21-day cumulative irritation study using 14 rabbits showed higher local tolerance of a skin cream containing 1% UR-4056 as compared to a commerc,ial cream containing 1% CL (irritation indexe~: 1.2 and 3.7, respectively, p < 0.01). When similar skin cream formulations containing 1% UR-4056 or 1% CL were compared, the irritation indexes were 1.6 for UR°4056 and 2.2 for CL. Histopathological findings confirmed the better local tolerance of 17o UR-4056 skin creams. Conclusion: UR-4056 (Prop INN: Flutrimazole) is a new imidazole antifungal agent ~ lving potent and broad spectrum of in vitro and in vivo activity, as well as very low dem-,al irritation potential.

Targetting of piperazine complexes in ascariasis Singh, G. and Sharma, S.N. Dept. of Pharmaceutics, Faculty of 2'harmacy, Jamia Hamdard Hamdard Nagar, New Delhi-l l O 062, India

Ascariasis is a common nematode infection in human beings. More than one fourth of the population of the world is affected by this disease. Piperazine is a safe drug in the treatment of ascariasis but presents certain li~J~ations on its use due to its bio-physico-chemical properties. Further it enhances extrapyramidal effects induced by tricychc antidepressants in epilepsy. A new piperazine complex has been synthesized having desirable pr~perties of an anthelmintic. Systemic absorption of the complex could be reduced to considerai31e extent thereby enhancing its therapeutic value. Tablets of the complex were formulated with success which on evaluation in vitro and in vivo proved both efficacy and safety. In asc~dasis, it is wished to target the drug in duodenum, jejunum ~:p~dileum with no