Isoconazole Nitrate Research Articles

Inflammatory tinea pedis with bacterial superinfection effectively treated with isoconazole nitrate and diflucortolone valerate combination therapy

Undetected tinea pedis in a patient with diabetes can lead to serious bacterial infections with potentially serious consequences, such as foot amputations. Here we report on a 60-year-old patient with diabetes presenting with pain, severe pruritus, and malodour in the foot's interdigital area, and subsequently, diagnosed with inflammatory tinea pedis with bacterial superinfection. The patient was successfully treated with Travocort cream containing isoconazole nitrate 1% and diflucortolone valerate 0.1%; marked improvement occurred within 5 days.

Effective treatment of tinea corporis due to Trichophyton mentagrophytes with combined isoconazole nitrate and diflucortolone valerate therapy

Trichophyton mentagrophytes is the dermatophyte species most commonly reported in cases of guinea pig-associated dermatophytosis (or guinea pig fungus) a condition that more often affects children than adults. In this case, a 13-year-old girl with recent direct contact with guinea pigs presented with a previously undertreated inflammatory skin lesion on the left side of her upper body, which was positive both for Trichophyton mentagrophytes and Staphylococcus epidermidis. The condition was subsequently diagnosed as tinea corporis due to Trichophyton mentagrophytes with concomitant bacterial infection and effectively treated with 2 weeks of twice-daily application of Travocort cream containing isoconazole nitrate 1% and diflucortolone valerate 0.1%. Visible improvement in the lesion was apparent after only 1 week of treatment.

New copper(II) complexes with isoconazole: Synthesis, structures and biological properties

There is an increasing demand for novel metal-based complexes with biologically relevant molecules in technology and medicine. Three new Cu(II) coordination compounds with antifungal agent isoconazole (L), namely mononuclear complexes [CuCl2(L)2] (1), and [Cu(O2CMe)2(L)2]·2H2O (2) and coordination polymer [Cu(pht)(L)2]n (3) (where H2pht –o-phthalic acid) were synthesized and characterized by IR spectroscopy, thermogravimetric analysis and X-ray crystallography. X-ray analysis showed that in all complexes, the isoconazole is coordinated to Cu(II) centres by a N atom of the imidazole fragment. In complex 1, the square-planar environment of Cu(II) atoms is completed by two N atoms of isoconazole and two chloride ligands, whereas the Cu(II) atoms are coordinated by two N atoms from two isoconazole ligands and two O atoms from the different carboxylate residues: acetate in 2 and phthalate in 3. The formation of an infinite chain through the bridging phthalate ligand is observed in 3. The biosynthetic ability of micromycetes Aspergillus niger CNMN FD 10 in the presence of the prepared complexes 1–3 as well as the antifungal drug isoconazole were studied. Complexes 2 and 3 accelerate the biosynthesis of enzymes (β-glucosidase, xylanase and endoglucanase) by this fungus. Moreover, a simplified and improved method for the preparation of isoconazole nitrate was developed.

Trichophyton mentagrophytes-associated Majocchi’s granuloma treated with cryotherapy

We here report the case of a woman with dermatophytosis of the thighs due to Trichophyton mentagrophytes where an unusual clinical picture posed considerable diagnostic and therapeutic problems. She presented numerous skin lesions located on the dorsolateral face of the left thigh and the medial surface of the right calf. The initial lesions consisted of small itchy pustules that evolved to exfoliation after scratching. Results of histopathologic examination ofa skin biopsy were consistent with dermatophytosis, although the negativity of PAS staining did not allow confirmation of this diagnosis. Direct microscopic examination with 10% KOH was negative; however, skin cultures on BioMerieux media revealed Tr. Mentagrophytes. Following the diagnosis of Trichophyton infection, the patient was treated with a combination of isoconazole nitrate and difluocortolone valerate. After therapy, both direct microscopic mycologic examination and culture on BioMerieux medium were negative; however, the lesions persisted, assuming a completely different aspect. Cryotherapy with liquid nitrogen was started. This led to a spectacular improvement: the surface of the skin became almost normal, merely showing slight discoloration. An unusual clinical presentation and non-responsiveness to treatment should prompt revision of the primary diagnosis. A negative result of direct microscopy should not exclude the diagnosis of dermatophytosis. Cryotherapy should be considered in cases that do not respond to conventional antifungal medication.

Non-invasive analysis of penetration and storage of Isoconazole nitrate in the stratum corneum and the hair follicles

Bacteria and fungi are located in the stratum corneum and the hair follicles. Therefore, the development and assessment of efficient drugs requires standard in vivo investigation methods permitting a differentiation between intercellular and follicular penetration and storage of topically applied anti-microbial substances.In the present study, the penetration and storage of Isoconazole nitrate in the stratum corneum and hair follicles was investigated by differential stripping after a 14-day topical application period and during a follow-up period of a further 21days.One week after the application had terminated, Isoconazole nitrate could still be detected in concentrations above the minimal inhibition concentration in the stratum corneum and the hair follicles. In some subjects, Isoconazole nitrate could even be detected 14days after the last application. No relevant changes in TEWL values were measured, indicating that the investigated compound did not induce an impairment of the barrier function.The study showed that differential stripping is suited to investigate the penetration and storage of topically applied substances into the stratum corneum and the hair follicles. Also, the hair follicles are a long-term reservoir for topically applied substances. This is of clinical importance, where a long-lasting therapeutic effect beyond the application time is required.

Study of the forced degradation of isoconazole nitrate in bulk drug and cream formulations

Bulk drug and cream formulations of isoconazole were subjected to the following ICH-recommended stress conditions: hydrochloric acid (0.1 M), sodium hydroxide (0.1 and 1 M), and hydrogen peroxide (3%). Photostability was monitored for 60 h in a UV chamber. Analysis of drug degradation was performed using an HPLC method that had been validated for linearity, range, precision, accuracy, limits of detection and quantification, and selectivity and robustness in accordance with the criteria established by Resolution 899 of the Brazilian National Health Surveillance Agency (ANVISA). When isoconazole cream was exposed to a light source, the isoconazole content decreased slightly, but no degradation products were formed as indicated by the absence of additional peaks in the HPLC chromatogram. The drug was found to be unstable in both the bulk form and in the cream formulation when subjected to alkaline hydrolysis conditions, exhibiting reductions of ca. 43 and 70% of the initial content, respectively. Different sample solutions that had been subjected to alkaline degradation indicated, through subsequent pH adjustments and UV analysis, the presence of an isosbestic point at 275 nm, suggestive of a reversible phenomenon in alkaline media. Reversibility by bringing the pH back to the initial value may be a valuable tool for identifying real degradation processes. In contrast to the drug's instability under alkaline conditions, isoconazole was found to be stable under both acid hydrolysis and oxidative conditions.

Dermatoses of fungal etiology in the anogenital area: errorsin the management and ways to eliminate them

The article discusses the most prevalent errors in the course of examining and treating patients with dermatoses in the anogenital area. Different forms of mycoses are diagnosed in 58% of male and 25% of female patients. Isoconazole (Travogen) demonstrated a high clinical efficacy for the treatment of dermatomycoses due to providing a high skin concentration of the active ingredient. Travocort, a combination drug comprising isoconazole nitrate and diflucortolone valerate, was indicated to treat patients with burdened allergic anamnesis and mixed infection (bacterial and fungal association) at the first stage of treatment to reduce the risk of developing complications in the form of eczematization.

The release of isoconazole nitrate from different suppository bases: in-vivo release of drug labelled with 99mTc in rabbits.

The influence of the suppository bases on the in-vivo release of 99mTc-labelled isoconazole nitrate was investigated. The single-dose vaginal suppository formulations for local treatment of vaginitis were prepared by a fusion method using polyethylene glycols, Witepsol H15, Novata BD and Cremao. Prepared vaginal suppositories containing solid-labelled substance were applied to the vagina of rabbits and at 0, 2 and 24 h after administration, the amounts of radioactivity in the vagina were detected by the SPECT Gamma Camera and the release rates of the drug were calculated. The percent released was found to be in the following order; polyethylene glycol (PEG) 6000 > PEG 4000 > Witepsol > PEG 1500 > Novata BD > Cremao. The results obtained in both in-vitro and in-vivo studies indicated that the vaginal suppository of isoconazole nitrate prepared with polyethylene glycols could confidently be used in therapy.

The release of isoconazole nitrate from different suppository bases: in-vitro dissolution, physicochemical and microbiological studies.

The influence of the suppository base on the in-vitro release of isoconazole nitrate was studied by dissolution, physicochemical diffusion and microbiological disk-diffusion methods. Vaginal suppository formulations containing 25 mg isoconazole nitrate for local treatment of vaginitis were prepared by a fusion method, using different hydrophilic and lypophilic suppository bases (PEG 6000, PEG 4000, PEG 1500, Witepsol H15, Novata BD and Cremao). In-vitro release rates were examined by dissolution, physicochemical diffusion and microbiological disk-diffusion methods. In the physicochemical investigations the pH indicators (pH 1-14) erythrosin B, thymol blue, bromocresol green, chlorophenol red, phenol red, and alkali blue were added to agar gels. The discs were placed onto the agar gels and 21 h later, the coloured zone diameters were measured. In the microbiological investigations, the discs were put on the inoculated plates with the suspension of Candida albicans (Institute Pasteur 628). The inoculated plates were incubated at 37 degrees C for 3 days, then the diameters of inhibition zones were measured. In the dissolution investigations release rates were in the order PEG 6000 > PEG 4000 > PEG 1500 > > Witepsol H15 > Cremao > Novata BD. The diffusion distance of isoconazole nitrate in the physicochemical investigation was in the order polyethylene glycols > Witepsol H15 > Novata BD. In the microbiological studies release rates were found with polyethylene glycols > Witepsol H15 > Novata BD > Cremao. The findings in the in-vitro studies suggested that polyethylene glycols are suitable bases for vaginal suppositories.

Liquid Chromatographic and Spectrophotometric Determination of Diflucortolone Valerate and Isoconazole Nitrate in Creams

A new RP-LC method and two new spectrophotometric methods, principal component regression (PCR) and first derivative spectrophotometry, are proposed for simultaneous determination of diflucortolone valerate (DIF) and isoconazole nitrate (ISO) in cream formulations. An isocratic system consisting of an ACE C18 column and a mobile phase composed of methanol-water (95 + 5, v/v) was used for the optimal chromatographic separation. In PCR, the concentration data matrix was prepared by using synthetic mixtures containing these drugs in methanol-water (3 + 1, v/v). The absorbance data matrix corresponding to the concentration data matrix was obtained by measuring the absorbances at 29 wavelengths in the range of 242-298 nm for DIF and ISO in the zero-order spectra of their combinations. In first derivative spectrophotometry, dA/dlambda values were measured at 247.8 nm for DIF and at 240.2 nm for ISO in first derivative spectra of the solution of DIF and ISO in methanol-water (3 + 1, v/v). The linear ranges were 4.00-48.0 microg/mL for DIF and 50.0-400 microg/mL for ISO in the LC method, and 2.40-40.0 microg/mL for DIF and 60.0-260 microg/mL for ISO in the PCR and first derivative spectrophotometric methods. These methods were validated by analyzing synthetic mixtures. These three methods were successfully applied to two pharmaceutical cream preparations.

Successful treatment of tinea pedis with a topical agent containing isoconazole nitrate and diflucortolone valerate

MycosesVolume 51, Issue s4 p. 48-49 Successful treatment of tinea pedis with a topical agent containing isoconazole nitrate and diflucortolone valerate Young-Chul Kye, Young-Chul Kye Department of Dermatology, Korea University Anam Hospital, Sungbuk-gu, Seoul, KoreaSearch for more papers by this author Young-Chul Kye, Young-Chul Kye Department of Dermatology, Korea University Anam Hospital, Sungbuk-gu, Seoul, KoreaSearch for more papers by this author First published: 28 August 2008 https://doi.org/10.1111/j.1439-0507.2008.01609.xCitations: 4 Young-Chul Kye, MD, PhD, Department of Dermatology, Korea University Anam Hospital, 126-1, 5-ga Anam-dong, Sungbuk-gu, Seoul 136-705, Korea.E-mail: [email protected] Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL No abstract is available for this article.Citing Literature Volume51, Issues4Special Issue: Superficial Dermatomycoses Worldwide: Multinational Treatment Experience with a Combination of Isoconazole Nitrate and Diflucortolone ValerateSeptember 2008Pages 48-49 RelatedInformation

The advantages of topical combination therapy in the treatment of inflammatory dermatomycoses

Dermatomycoses are contagious superficial fungal infections, which are highly prevalent in developed and developing countries. Caused by a range of Epidermophyton, Microsporum and Trichophyton species, dermatomycoses manifest on glabrous skin as 'ringworm', an annular scaly lesion with a variable inflammatory component. Itch is the chief subjective symptom, particularly in tinea cruris. Unless lesions are extensive or resistant to local therapy, dermatomycoses of glabrous skin are treated with topical antifungal agents, such as imidazoles and allylamines. Studies show, however, that the addition of a topical corticosteroid to imidazole therapy increases the bioavailability and prolongs the activity of the antimycotic, while rapidly reducing inflammatory symptoms. Travocort is a combination of 1% isoconazole nitrate (ISN), a broad-spectrum imidazole with established antimicrobial activity and antimycotic efficacy, and 0.1% diflucortolone valerate (DFV), a potent topical corticosteroid with low systemic absorption and therefore a low risk of systemic glucocorticoid side-effects. In randomised, double-blind controlled clinical trials, Travocort therapy showed a more rapid onset of action, faster relief of itch and other inflammatory symptoms, improved overall therapeutic benefits and better mycological cure rate during the first 2 weeks of treatment compared with ISN monotherapy. Travocort is well tolerated and, because of prolonged ISN retention in the skin, provides antifungal protection against reinfection for some weeks after therapy.

Superficial Dermatomycoses Worldwide: Multinational Treatment Experience with a Combination of Isoconazole Nitrate and Diflucortolone Valerate

Superficial Dermatomycoses Worldwide: Multinational Treatment Experience with a Combination of Isoconazole Nitrate and Diflucortolone Valerate

The effective use of isoconazole nitrate and diflucortolone valerate cream in the treatment of inguino‐femoral skin fold mycosis

The effective use of isoconazole nitrate and diflucortolone valerate cream in the treatment of inguino‐femoral skin fold mycosis

Treatment of candidal intertrigo with a topical combination of isoconazole nitrate and diflucortolone valerate

Treatment of candidal intertrigo with a topical combination of isoconazole nitrate and diflucortolone valerate

Tinea corporis treated with a combined topical therapy containing isoconazole and a corticosteroid

MycosesVolume 51, Issue s4 p. 37-38 Tinea corporis treated with a combined topical therapy containing isoconazole and a corticosteroid Jaco Jürgens, Jaco Jürgens General Practitioner, Krugersdorp, Gauteng, South AfricaSearch for more papers by this author Jaco Jürgens, Jaco Jürgens General Practitioner, Krugersdorp, Gauteng, South AfricaSearch for more papers by this author First published: 28 August 2008 https://doi.org/10.1111/j.1439-0507.2008.01610.xCitations: 3 Dr Jaco Jürgens, General Practitioner, Krugersdorp, Gauteng, South Africa.E-mail: jacojuhl@gmail.com Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article.Citing Literature Volume51, Issues4Special Issue: Superficial Dermatomycoses Worldwide: Multinational Treatment Experience with a Combination of Isoconazole Nitrate and Diflucortolone ValerateSeptember 2008Pages 37-38 RelatedInformation

Pustular allergic contact dermatitis to isoconazole nitrate

The topical imidazole antimycotics are widely used and are an infrequent cause of contact allergy. We report on a woman, who developed an unusual clinical picture of allergic contact dermatitis, namely papulopustular reaction, evoked by an isoconazole nitrate-containing cream. The histopathologic changes included subcorneal pustules, spongiosis, and an inflammatory infiltrate composed mainly of lymphocytes and some eosinophils and neutrophils. The patient demonstrated a severe vesicular reaction to isoconzole nitrate as is and at an imidazoles concentration of 0.5%. No cross-reactivity with other imidazole antimycotics was noted.

Activity of topically applied leukotriene B4 in experimental dermatophytosis

In a pilot study to assess the antimycotic potential of the chemoattractant leukotriene B4 (LTB4), guinea pigs were infected with Trichophyton mentagrophytes var. mentagrophytes and divided into groups of untreated control animals or treated daily with LTB4, isoconazole nitrate or vehicle alone. The animals were assessed clinically, mycologically and histopathologically. Treatment with isoconazole nitrate was the most effective. The LTB4-treated group were clinically worse than the non-treated group and the mycological results remained positive throughout the assessment period.

Diflucortolone valerate. Asian experience.

More than 10 years ago, diflucortolone valerate (Nerisone, Nerisona) was introduced in Germany and soon after in Asian countries in a concentration of 0.1% in cream, ointment and fatty ointment bases. 897 patients were included in the first Southeast Asian multicentre trial with these 3 formulations, and good efficacy and tolerability combined with a rapid onset of effect were shown. These results were confirmed later in Indonesia in an extended follow-up trial which included 1295 patients. A combination of 0.1% diflucortolone valerate with 1.0% chlorquinaldol was introduced after a multicentre Southeast Asian trial involving 8668 patients with inflammatory or allergic skin conditions for which a supplementary anti-infective treatment, for prophylaxis or therapy, was considered to be indicated. Excellent results were obtained in terms of efficacy, tolerability and cosmetic properties. A randomised double-blind trial comparing this preparation with a so-called 'shotgun' combination containing 0.05% betamethasone 17-valerate, 0.1% gentamicin, 1.0% tolnaftate and 1.0% clioquinol in 288 patients in the Philippines resulted in a better efficacy for the diflucortolone preparation in the 80 patients with bacterially or mycotically infected skin diseases. A 0.3% concentration of diflucortolone valerate was developed and introduced as a high potency topical corticosteroid. A trial in the Philippines which involved 143 patients with mostly severe chronic recurrent and resistant corticosteroid-responsive skin disease confirmed a pronounced clinical efficacy with a low incidence of side effects. For the treatment of inflammatory or eczematised dermatomycosis. 0.1% diflucortolone was combined with 1.0% isoconazole nitrate (Travocort). In a randomised double-blind study of 294 patients in Thailand, this preparation was compared with a plain 1.0% clotrimazole formulation. The results were significantly better for the diflucortolone plus isoconazole nitrate combination in terms of remission of symptoms, and after 1 week the mycological cure rates were also better, as shown in potassium hydroxide and culture investigations. It is concluded, therefore, that diflucortolone valerate in the available galenic bases and in effective combinations with other agents has been proven in extensive clinical trials to be a valuable therapeutic tool in dermatological practice.

The retention of isoconazole in the skin after once or twice daily application of 1% isoconazole nitrate cream (Travogen) over a 14-day period.

Summary The concentration of the antimycotic agent isoconazole nitrate was measured in the horny layer and in skin tissues after once or twice daily topical applications of 1% isoconazole nitrate cream to the volar aspect of both arms in 12 volunteers. No difference in drug levels either within the horny layer or whole skin were found between the treatments. From this evidence it is anticipated that a once daily treatment regimen would be as clinically effective as a twice daily-treatment regimen. High levels of the drug were found in the horny layer 10 days after the end of both treatments. This large and long lasting reservoir of the drug in the horny layer may provide protection of the skin against new infection for some time after treatment.