Experimental studies in vitro and in vivo on the mutagenicity of flavoxate.

Flavoxate HCl is a drug with a remarkable smooth muscle relaxant activity, selective for the genito-urinary tract. In order to verify its safety the following mutagenic tests have been effected: gene reversion in S. typhimurium, gene conversion and crossing-over on S. cerevisiae 6117, micronucleus test and DNA-repair on B. subtilis. In our experimental conditions, flavoxate HCl was found to be devoid of potential mutagenic activity.

The quantitative determination of neomycin sulphate by a diffusion technique on agar plates by the method of the European Pharmacopoeia, 2nd edition--evaluation of precision and reproducibility of the method.

The medium recommended by the European Pharmacopoeia (EP), 2nd edition, for the microbiological determination of neomycin by the agar diffusion method was tested and compared with the medium recommended by the EP, 1st edition. The tests were carried out in different laboratories. The medium recommended by the EP, 2nd edition, gave greater precision and reproducibility than the previous medium. The possibility of using a reference standard of almost pure neomycin B for both the determination of framycetin and neomycin was evaluated. The results demonstrated that the medium recommended by the EP, 2nd edition, gave better precision and reproducibility. Difficulty in achieving valid assays was practically the same with both media.

Mutagenicity studies on denzimol, a new anticonvulsant drug.

N-[beta-[4-(beta-Phenylethyl)phenyl]-beta-hydroxyethyl] imidazole hydrochloride (denzimol, Rec 15-1533), a new anticonvulsant drug, was tested using the Ames procedures with and without metabolic activation, on five strains of Salmonella tythimurium and using the host mediated assay with Schizosaccharomyces pombe as microorganism test. In both tests the drug did not show any mutagenic activity when compared with mutagenic standards.

Mutagenicity studies on tibezonium, a new oropharyngeal disinfectant.

N,N-Diethyl-N-methyl-[2-[[4-(4-phenylthio) phenyl]-3H-1,5-benzodiazepin-2-yl]thio]-ethanaminium iodide) (tibezonium iodide; CAS-54663-47-7), a new oropharyngeal disinfectant, was tested, using the Ames procedure with and without metabolic activation, on five strains of Salmonella typhimurium and using the host mediated assay with Schizosaccharomyces pombe as microorganism test. In both tests the drug did not show any mutagenic activity when compared with mutagenic standards.

The Salmonella mutagenicity assay on fenticonazole, a new antifungal imidazole derivative.

alpha-(2,4-Dichlorophenyl)-beta,N-imidazolylethyl 4-phenylthiobenzyl ether nitrate (fenticonazole, Rec 15/1476), a new potent antibacterial and antifungal imidazole derivative, was tested for mutagenicity in the Salmonella reversion assay developed by Ames et al. Fenticonazole was found to be negative for strains TA 1535, TA 1537, TA 1538, TA 98, TA 100 with and without microsomal activation.

Fenticonazole, a new imidazole derivative with antibacterial and antifungal activity. In vitro study.

The activity of alpha-(2,4-dichlorophenyl)-beta,N-imidazolylethyl 4-phenylthiobenzyl ether nitrate (fenticonazole, Rec 15/1476) compared with those of reference drugs, was tested in vitro on various bacteria and fungi. This compound showed in vitro an excellent activity against gram-positive microorganisms. The antifungal activity spectrum is very broad: dermatophytes, yeasts and dimorphic fungi were the most susceptible organisms. Fenticonazole showed in vitro at pH range 4-5 the highest activity against yeasts. The addition of inactivated bovine serum to the culture medium led to a slight decrease in activity of all the tested substances.

Antifungal activity of fenticonazole in experimental dermatomycosis and candidiasis.

The antifungal activity of alpha-(2,4-dichlorophenyl)-beta,N-imidazolylethyl 4-phenylthiobenzyl ether nitrate (fenticonazole, Rec 15/1476) in experimental dermatomycosis and candidiasis in guinea pigs was studied. Fenticonazole proved to be a very active drug with a healing capacity generally higher than that of the reference compounds. The adequate range of activity was from 1% to 3%, giving complete healing without relapses in 100% of cases treated. Fenticonazole is presently undergoing further experimental studies and on the basis of our results a clinical trial would therefore seem to be essential.

Mutagenicity studies on fenticonazole, a new antifungal imidazole derivative.

The forward mutational assay on Schizosaccharomyces pombe and the mitotic gene conversion assay on Saccharomyces cerevisiae were performed in order to verify whether alpha-(2,4-dichlorophenyl)-beta,N-imidazolylethyl 4-phenylthiobenzyl ether nitrate (fenticonazole, Rec 15/1476) shows a potential mutagenicity. In both tests the drug does not seem to possess any mutagenic activity when compared with mutagenic standards.

Effects of different drugs on the urinary excretion of nifurpipone (NP) and of nitrofurantoin (NTF) in the rat.

A study was made on possible interferences of several drugs on the urinary excretion of nifurpipone and of nitrofurantoin orally administered to rats. Phenobarbital, a microsomial enzyme inducer, SKF 525 A, a microsomial enzyme inhibitor, probenecid, an inhibitor of the tubular acid secretory system, quanine, an inhibitor of the tubular alkaline secretory system, and hydrochlorothiazide, a diuretic, were studied. None of these treatments altered in an important way the urinary excretion of nifurpipone or of nitrofurantoin.