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The aim of the present work was to develop a promising drug delivery system of oxiconazole nitrate-loaded solid lipid nanoparticles (SLNs) topical gel to enhance the drug effectiveness for the treatment of Tinea infection. SLNs were prepared by emulsification-solvent evaporation method. Particle size and entrapment efficiency of the prepared SLNs were investigated. An appropriate formulation was selected and examined for morphology and physicochemical characterization adopting Scanning electron microscope and Differential scanning colorimetry. In-vitro drug release was also investigated. The selected SLNs were loaded into 1% Carbopol 934 gel that was investigated for homogeneity, pH, grittiness, spreadability, viscosity and

A clinical trial was carried out for the duration of six months from September' 2012 to February' 2013 in the Department of Dermatology and Venereology, Shaheed Monsur Ali Medical College, Uttara Dhaka and patients attending private clinical chamber. To evaluate the effectiveness of oxiconazole cream in comparison to the ketoconazole cream for the treatment of inguinocrural dermatophytoses.A total number of 60 patients with inguinocrural dermatophytoses were included in the study of which 30 patients were treated with oxiconazole (Group A) and the rest 30 patients were treated with ketoconazole (Group B)once daily for 21 days and weekly the outcome of lesions were clinically evaluated and recorded.In group A, male and female were 17 (56.7%) cases and 13 (43.3%) cases respectively. In group B, male and female were 16 (53.3%) cases and 14 (46.7%) cases respectively.The mean age with SD in group A and group B were 28.93 ± 8.29 years and 31.36 ± 8.36 years respectively. The mean scoring with SD in group A and group B were 6.26 ± 2.22 minutes and 6.53 ± 1.81 minutes respectively at the time of observation and 4.23 ± 1.50 minutes and 5.13 ± 1.45 minutes respectively after 1 week and 2.00 ± 1.22 minutes and 3.25 ± 1.07 minutes respectively after 2 weeks. The difference between the mean score of the two group is significant (p=0.006). The mean scoring with SD in group A and group B were 0.00 ± 0.00 minutes and 1.75 ± 0.95 respectively after 3 weeks.Sotopical treatment oxiconazole has revealed itself to be as efficient as ketoconazole and it seems more effective and better tolerated than ketoconazole.Medicine Today 2016 Vol.28(2): 57-61

A series of novel, bioactive 5-substituted indole-2-carboxamide derivatives (10a–t and 14a–k) are synthesized by the coupling of 5-substituted indole-2-carboxylic acids with various amines in the presence of EDC HCl/HOBt in DMF/CH2Cl2 as a solvent. In vitro, antibacterial activity of titled compounds against pathogenic bacteria Klebsiella pneumoniae, Escherichia coli, Pseudomonas aeruginosa, Salmonella typhi and antifungal activity against pathogenic fungi Candida albicans, Cryptococcus neoformans, Aspergillus fumigatus, and Candida parapsilosis are evaluated using gentamicin/ciprofloxacin and fluconazole/oxiconazole as standard drugs, respectively. The majority of the synthesized compounds exhibited good antibacterial activity, but surprisingly none showed antifungal activity. Compounds 10c, 10d, 10i, 10j, 10l–n, 14g, 14h, 14i, 14j, and 14k exhibited high inhibitory antibacterial activity with MIC values in the range of 0.12–6.25 µg/mL. Interestingly, compounds 14i, 14j, and 14k exhibited excellent antibacterial activity against K. pneumoniae and E. coli compare to synthesized compound. All the experimental results promote us to consider this series as a starting point for the development of novel and more potent antibacterial agents in the future.

Background : Dermatophytosis is a geographically widespread group of fungal infections. Tinea corporis and tinea cruris are the most common dermatophytoses in Bangladesh. Oxiconazole has recently been introduced in Bangladesh in the treatment of dermatophytoses. Objective : To evaluate the efficacy of topical 1% oxiconazole cream once daily in the treatment of tinea corporis and tinea cruris. Materials and Methods : A clinical trial was carried out in the department of Dermatology and Venereology, Jalalabad Ragib-Rabeya Medical College Hospital, Sylhet on 81 patients with tinea corporis and/or tinea cruris. The patients were instructed to apply 1% oxiconazole cream once daily for 2 weeks with clinical assessment made at weekly intervals during treatment period. Results : The mean age of the patients was 32.5 ± 10.5 years, with tinea corporis in 47 (58.0%) patients and tinea cruris in 34 (42.0%). The mean clinical assessment score declined from 6.6 ± 1.3 at baseline to 3.9 ± 1.2 at week 1, 0.9 ± 1.3 at week 2 and 0.7 ± 1.1 at week 4. Reduction of clinical assessment score from baseline to end of the treatment period was statistically significant (p

Oxiconazole loaded Unsaturated Fatty Acid Liposomes (UFL) was used as a transdermal formulation in treatment of chronic fungal infections. Oxiconazole has low oral bioavailability of drug and short half-life that’s why preferring this transdermal route for proper treatment against fungal infections. UFL was made by using oleic acid and tween 80 in different proportion, batches were developed by using a central composite design. The optimal UFL-6 formulation has shown maximum entrapment efficiency (61.05%) and good vesicle size (215 nm). The oxiconazole release from UFLG-6 gels, follow Higuchi model and drug permeation via a cellophane membrane was maximum in comparison to other gel formulations. The UFLG-6 formulation also shows maximum antifungal activity against Candida albicans fungus.

Medications should be employed with caution in women of childbearing age who are pregnant or considering pregnancy. Compared to oral or parenteral agents, topical medications have limited systemic absorption and are deemed safer. However, their safety profile must be assessed cautiously due to the limited available data. In this article, we aggregate human and animal studies to provide recommendations on utilizing topical antiviral and antifungal medications in pregnancy. For antiviral medications, acyclovir and trichloroacetic acid are safe to use in pregnancy. Docosanol, imiquimod and penciclovir are likely safe, but should be utilized as second-line agents. Podofilox and podophyllin resin should be avoided. For antifungal medications, clotrimazole, miconazole and nystatin are considered first-line agents. Butenafine, ciclopirox, naftifine, oxiconazole and terbinafine may be utilized after the above agents. Econazole should be avoided during the first trimester and used sparingly during 2nd and 3rd trimester. Ketoconazole and selenium sulphide are likely safe, but should be employed in limited areas for brief periods.

Antifungal activity and in vitro inhibition time for sertaconazole (STZ) and 9 other topical drugs, namely amorolfine, bifonazole, clotrimazole, econazole, ketoconazole, miconazole, oxiconazole, terbinafine, and tioconazole were determined against 124 clinical isolates of dermatophyte (12 species) fungi by the microdilution method in a liquid medium and the measurement of optical density. STZ’s antifungal activity was not always affected by the tested dermatophyte genus, as was the case with the remaining antifungals. In vitro antifungal activity was at the same level for all the studied azole derivatives, but, in terms of partial inhibitory concentrations, STZ starts its in vitro inhibitory activity in a shorter time than the other tested substances, particularly in those incubation periods when the growth of the dermatophyte fungi was more developed.

The ‘click synthesis’ of some oxiconazole analogs 5a–5v having 1H-1,2,3-triazolyl residues by Huisgen cycloaddition was achieved in four steps (Scheme 1). Oximation of phenacyl chloride (1) followed by azidation of 2-chloro-1-phenylethanone oxime (2) provided azido ketoxime 3. The CuI-catalyzed Huisgen cycloaddition of 3 with terminal alkynes gave the 4-substituted (at the triazole) 2-(1H-1,2,3-triazol-1-yl)-1-phenylethanone oximes 4a–4i. The O-alkylation of 4a–4i with various alkyl halides resulted in the formation of the target molecules 5a–5v in good yields.

The syntheses of some novel carboacyclic nucleosides, 17a–17o, containing oxiconazole-like scaffolds, are described (Schemes 1–3). In this series of carboacyclic nucleosides, pyrimidine as well as purine and other imidazole derivatives were employed as an imidazole successor in oxiconazole. These compounds could be prepared in good yields by using two different strategies (Schemes 1 and 2). Due to Scheme 1, the N-coupling of nucleobases with 2-bromoacetophenones was attained for 18a–18e, and their subsequent oximation affording 19a–19e and finally O-alkylation with diverse alkylating sources resulted in the products 17a–17g, 17n, and 17o. In Scheme 2, use of 2-bromoacetophenone oximes 20, followed by N-coupling of nucleobases, provided 19f–19j whose final O-alkylation produced 17h–17m (Scheme 2). For the rational interpretation of the dominant formation of (E)-oxime ethers rather than (Z)-oxime isomers, PM3 semiempirical quantum-mechanic calculations were discussed and the calculations indicated a lower heat of formation for (E)-isomers.

Zusammenfassung: Autoradiographische Untersuchungen und die horizontale Schnittmethode nach Exposition in der Penetrationskammer erganzen sich in der Aussage, das nach Anreiche-rang in der Homschicht eine stetige Diffusion durch die Epidermis zum Corium in der Form sich entwickelt, das im unteren Corium noch eine chemotherapeutisch wirksame Anreicherung crfolgt. Oxiconazol wird auch uber den Haarfollikel resorbiert und zeigt damit eine Perme-ationskinetik, die eine lokale Anwendung des Praparates Myfungar als vollig ausreichend fur die Behandlung von Dermatomykosen ausweist. Summary: Autoradiographic and sectioning techniques after topical application of 14-C Oxiconazol in Myfungar-Creme in vitro give additional results of an enrichment of Oxiconazol in the deeper layers of epidermis and hair follicles. The concentration also in the upper corium and in the deeper follicles displays concentrations which have fungistatic effectivity.

Summary: In a total of 204 patients with dermatomycosis and erythrasma, oxiconazole (Oceral Roche, producer Hoffmann—La Roche AG, Grenzach-Wyhlen, (n = 105) and bifonazole (n = 99) were tested in a double—blind, randomized multicenter study. Both preparations were compared in regard to efficacy and tolerance. The period of treatment in both groups was 25 days on average. Mycological sanitation and clinical healing was seen in 81 % and 86 % of these cases respectively. Tolerance has been judged as excellent in 70 % and 71 % of all patients respectively. Local intolerances were noticed in 1 % and 4 % of all patients respectively. Both preparations can be regarded as equally effective and tolerable. Zusammenfassung: An insgesamt 204 Patienten mit Dermatomykosen und Erythrasma wurden Oxiconazol* (n = 105) und Bifonazol (n = 99) im Rahmen einer doppelblinden, randomisierten, multizentrischen Prufung untersucht. Beide Pra parate wurden hinsichtlich Wirksamkeit und Vertraglichkeit verglichen. Die Therapiedauer betrug in den zwei Kollektiven im Mittel 25 Tage. Die mykologische Sanierung und klinische Heilung wurde in 81% bzw. 86 % der Falle erreicht. Die Vertraglichkeit wurde bei 70% aller Patienten als ausgezeichnet beurteilt. Lokale Unvertraglichkeiten traten bei 1% bzw. 4% der Patienten auf. Beide Praparate konnen als gleich gut wirksam und vertraglich bezeichnet werden.

Three cases of opportunistic cutaneous aspergillosis caused by Aspergillus chevalieri are described. The lesions were erythematous and hyperkeratotic with vesicopapular eruptions and scaling. Histopathology revealed granulomatous reaction showing polymorphonuclear leucocytes around fungal hyphae, which were broad, septate, branched and aggregated in the epidermal area. Oxiconazole and amorolfine, with a minimum inhibitory concentration of 10 micrograms ml-1, were the most active drugs against A. chevalieri 'in vitro'. A. chevalieri is, for the first time, documented as opportunistic pathogen of man.

Zusammenfassung: An insgesamt 144 Patienten, die an Dermatomykosen bzw. Pityriasis versicolor litten, wurden Oxiconazol*-Creme bzw. -Losung bezuglich Wirksamkeit und Vertraglichkeit untersucht. Die Anwendung erfolgte bei 73 Patienten nur 1 x taglich, bei 71 Patienten 2 x taglich. Die Therapiedauer betrug in beiden Kollektiven im Durchschnitt 3 bis 4 Wochen. Weder hinsichtlich Wirksamkeit noch hinsichtlich Vertraglichkeit konnte ein Unterschied zwischen beiden Patientengruppen ermittelt werden. Somit wird mit der einmal taglichen Applikation von Oceral Roche der gleiche Therapieerfolg erzielt wie mit der zweimal taglichen Applikation. Summary: Oxiconazole cream or solution was tested for efficacy and tolerability in a total of 144 patients suffering from dermatomycosis or tinea versicolor. 73 patients received the treatment only once daily and 71 twice daily. In both groups the treatment lasted on an average 3–4 weeks. No difference was found between the two populations with respect to efficacy or tolerability. We may conclude that a single daily application of Oceral Roche provides the same therapeutic success as the twice daily application.

Summary: Short-term experiments on excised skin (human, pig) gave the following results: 1. In the tissue activity test with direct inoculation (D-TAT) commercial preparations of the non-azole antimycotics ciclopiroxolamine, tolnaftate and naftifine, produced higher inhibitory activity against Trichophyton mentagrophytes (standard strain) in various levels of the horny layer than were produced by the azole antimycotics econazole, miconazole, clotrimazole, oxiconazole and bifonazole. Fast drying solutions of antimycotics invariably gave higher inhibitory activities than creams. In the ultrafiltration tissue activity test (UFT- TAT) against Candida albicans (2 strains), antimycotic agents ranked in order of effectiveness as follows: ciclopiroxolamine – most of the azole antimycotics – bifonazole and naftifine. 2. In tests of fungicidal activity against T. mentagrophytes (2 strains) and Microsporum gypseum (1 strain) the first step was to inoculate the skin surface. After the horny layer had been penetrated by fungal mycelia, antimycotic agents of documented fungicidal potency, chiefly in the form of creams, were applied to the skin surface and left to act for up to 18 hours. The horny layer and epidermis were then scraped off and the concentration of viable fungi was determined. Ciclopiroxolamine cream and lotion produced by far the greatest diminution in viable fungi; creams containing oxiconazole and naftifine were moderately effective and those containing tioconazole and bifonazole produced a relatively small decrease in viable fungi. To avoid erroneous results it is important to homogenize and dilute the skin scrapings; if this is not done certain antimycotics will give misleadingly high fungal killing rates. At this early stage the scatter of results is still wide and minor differences in efficacy cannot as yet be detected with certainty. 3. From the results of various comparative tests it is evident that pig skin can be used as a substitute for human skin in the tests listed under 1. and 2. above. This discovery may make a valuable contribution towards limiting the need for experiments on living animals and trials on human beings. Zusammenfassung: In Kurzzeitversuchen an exzidierter Haut (Mensch, Schwein) wurde gefunden: 1. Im Gewebeaktivitatstest mit direkter Inokulation (D-GAT) wurde mit Handelspraparaten der Nichtazol-Antimykotika Ciclopiroxolamin, Tolnaftat und Naftifin in verschiedenen Hornschichtniveaus eine hohere Hemmaktivitat gegenuber Trichophyton mentagrophytes (Standard-Stamm) erzielt als mit solchen der Azol-Antimykotika Econazol, Miconazol, Clotrimazol, Oxiconazol und Bifonazol. Rasch trocknende Losungen von Antimykotika ergaben durchweg hohere Hemmaktivitaten als Cremes. Im Ultrafiltrations-Gewebeaktivitatstest (UFT-GAT) gegenuber Candida albicans (2 Stamme) ergab sich nach erzielter Wirksamkeit die Rangfolge Ciclopiroxolamine – Mehrzahl der Azolantimykotika – Bifonazol und Naftifin. 2. In Fungizidie-Testen gegenuber T. mentagrophytes (2 Stamme) und Microsporum gypseum (1 Stamm) wurde zunachst die Hautoberflache inokuliert. Nach Durchdringung der Hornschicht mit Pilzmyzelien wirkten auf die Hautoberflache bis zu 18 Stunden lang uberwiegend Cremes von als fungizid publizierten Antimykotika ein. Wahrend sich in abgeschabter Hornschicht und Epidermis der so bearbeiteten Hautoberflachen mit Ciclopiroxolamin-Creme und -Lotion die weitaus hochste Verminderung lebensfahiger Keime ergab, bewirkten Cremes mit Oxiconazol und Naftifin eine mittlere und solche mit Tioconazol und Bifonazol eine relativ niedrige Keimeliminierung. Zur Vermeidung von fehlerhaften Ergebuissen musten Homogenisierung und Verdunnung der Hautschabsel erfolgen, anderenfalls bei mehreren Antimykotika eine zu hohe Keimabtotung vorgetauscht worden ware. Wegen der vorerst noch hohen Streuung der Ergebnisse konnen kleinere Wirksamkeitsunterschiede noch nicht sicher erfast werden. 3. Nach dem Ergebnis verschiedener Vergleichstests kann in den Testen zu 1. und 2. Schweinehaut als Ersatz fur Haut vom Menschen dienen und durfte damit wesentlich zur Einschrankung von Versuchen am lebenden Tier und von Prufungen am Menschen beitragen.

Summary: 120 patients with dermatomycoses were treated topically with oxiconazole, a new antifungal imidazole, or with econazole according to a double-blind randomized order. Treatment was continued until one week after resolution of symptoms and assessment of results was based on both clinical and mycological parameters. 90% of the oxiconazole-treated patients, and 91.4% of those treated with econazole were cured. Tolerance was good in both groups. It was concluded that the antifungal effect of oxiconazole is comparable to that of econazole. Zusammenfassung: 120 Patienten, die an Dermatomykosen litten, wurden topisch mit Oxikonazol, einem neuen antimykotischen Imidazol-Derivat oder mit Econazol im Doppelblind-Verfahren behandelt. Die Behandlung wurde noch eine Woche nach Abklingen der klinischen Symptome fortgesetzt. Die Gesamtbeurteilung des Behandlungsresultates bei der Abschlusuntersuchung wurde sowohl auf klinische als auch auf mykologische Kriterien bezogen. 90% der Falle, die mit Oxiconazol und 91,4% von den Patienten, die mit Econazol behandelt wurden, waren geheilt. Die Vertraglichkeit war in beiden Gruppen gut. Die vorliegenden Ergebnisse zeigen, das die antimykotische Wirkung von Oxiconazol vergleichbar mit der von Econazol ist.

Summary: Amorolfin (Roche 14–4767/002) is a phenylpropyl-morpholine with a remarkable inhibitory effect on yeasts, dermatophytes, and other filamentous fungi. The pathological changes on the ultrastructure of Candida albicans blastospores produced by amorolfin are demonstrated by transmission electronmicroscopy. A comparison with untreated Candida cells as well as those treated with the imidazole compound oxiconazole was performed. Zusammenfassung: Amorolfin (Roche 14–4767/002) ist ein Phenylpropyl-Morpholin mit einer bemerkenswerten Hemmwirkung auf Hefen, Dermatophyten und andere Fadenpilze. Es werden die Amorolfin-bedingten Schadwirkungen auf die Ultrastruktur von Candida albicans-Blastosporen transmissionselektronenmikroskopisch im Vergleich mit unbehandelten und Oxiconazol-behandelten Zellen dargestellt.

Contact sensitization to azole antimycotics is rare, even though they are widely used. We present the case of a man who developed allergic contact dermatitis due to topical application of a variety of antimycotics. Patch testing revealed positive reactions to clotrimazole, croconazole, oxiconazole and tioconazole. Cross-sensitivity was possible, but multiple sensitizations could not be excluded.

A series of 8,9-disubstituted adenines (4, 5, 8), 6-substituted aminopurines (10-13) and 9-(p-fluorobenzyl/cyclopentyl)-6-substituted aminopurines (16, 17, 19-30) have been prepared and the antimicrobial activities of these compounds against Staphylococcus aureus, methicillin-resistant S. aureus (MRSA, standard and clinical isolate), Bacillus subtilis, Escherichia coli and Candida albicans were evaluated. 6-[(N-phenylaminoethyl)amino]-9H-purine (12) which has no substitution at N-9 position and 9-cyclopentyl-6-[(4-fluorobenzyl)amino]-9H-purine (24) exhibited excellent activity against C. albicans with MIC 3.12 microg/mL. These compounds displayed better antifungal activity than that of standard oxiconazole. Furthermore, compound 22 carrying 4-chlorobenzylamino group at the 6-position of the purine moiety exhibited comparable antibacterial activity with that of the standard ciprofloxacin against both of the drug-resistant bacteria (MRSA, standard and clinical isolate).

Herein,wereportthesynthesisandinvitroantimycoticac-tivityofsomeoximeandoximeetherderivativesofazole1,4-benzothiazine 3a–g and 4a–g related to Oxiconazole and toourpreviouslysynthesizedcompounds.Theaimwastoextendthe current structure–activity relationship(SAR) ofC. albicansCYP51 inhibitors by investigating the effect of partially con-straining the molecule through the insertion of oxime andoximeethergroups.Oxiconazole (Oxistat)

Summary Background Conventional therapy of onychomycosis is prolonged and often frustrating, which is why combination therapy involving topical, oral and surgical measures has been advocated as the treatment of choice. There are no controlled studies evaluating the efficacy of nail avulsion followed by topical antifungal therapy. Objectives To evaluate the efficacy of combined surgical and topical therapy for onychomycosis. Methods Forty patients with single nail onychomycosis [28 with distal and lateral subungual onychomycosis, seven with total dystrophic onychomycosis (TDO) and five with proximal subungual onychomycosis] were randomly assigned to four treatment groups. Each group received avulsion of the involved nail, followed by ketoconazole 2% cream without (group I) or with occlusion (group II), or oxiconazole 1% cream without (group III) or with occlusion (group IV). Topical therapies were applied twice daily. The patients were reviewed monthly and treatment was continued until the regrowth of completely normal nail (mycologically negative). In cured cases, further monthly review was carried out for at least 6 months, without any form of therapy. At each visit direct microscopic examination was repeated. Results There was a high dropout rate, with seven patients (group I), six patients (group II), six patients (group III) and eight patients (group IV) completing the treatment protocol. Out of these, mycological cure was achieved in three (43%) patients in group I, four (67%) in group II, two (33%) in group III and six (75%) in group IV. All the cases of TDO failed to respond to this therapy. Overall, 15 of 27 (56%) patients were cured with this approach. On further follow up, recurrence of onychomycosis was recorded in two patients in group I. No side-effects or long-term complications of the nail avulsion were encountered. Important limitations encountered in the present study included a small sample size, a high dropout rate (32%) and poor patient compliance. Conclusions Contrary to earlier reports, surgical nail avulsion with topical antifungal agents was not found to be a very encouraging modality for the treatment of onychomycosis. Both oxiconazole and ketoconazole delivered comparable results. Occlusion improved the treatment outcome, although the difference was not statistically significant. As a subtype, TDO showed poorest response. Surgical nail avulsion followed by topical antifungal therapy cannot be generally recommended for the treatment of onychomycosis.

OBJECTIVES The aim of this study has been to evaluate patients with tinea pedis for their demographic data and attitudes affecting the treatment of disease, and to compare the in vitro activity of 10 antifungal agents and to relate them to their in vivo activity. METHODS Patients with positive mycological examination were enrolled in the study, and a questionnaire comprised of 22 questions was administered. A mycological culture was carried out for each specimen. The antifungal susceptibility of the subcultured species was determined for griseofulvin, terbinafine, ciclopiroxolamine, fluconazole, ketoconazole, itraconazole, bifonazole, sulconazole, oxiconazole and miconazole with microdilution. RESULTS Mycological cultures were carried out from 59 patients and there were 35 positive cultures (59.3%). The dermatophytes were Trichophyton rubrum (n = 25) and Trichophyton mentagrophytes (n = 3). The yeasts were Candida albicans (n = 7), Candida glabrata (n = 1) and Trichosporon (n = 2). In the minimum inhibitory concentration (MIC) study, the mean +/- standard error of the mean (SEM) MICs of the antifungals for T. rubrum were as follows: terbinafine 0.01 +/- 0.003, oxiconazole 0.16 +/- 0.05, sulkonazole 0.31 +/- 0.05, miconazole 0.45 +/- 0.15, itraconazole 0.74 +/- 0.01, ketokonazole 1.03 +/- 0.17, ciclopiroxolamine 1.30 +/- 0.12, bifonazole 1.94 +/- 0.51, griseofulvin 4.87 +/- 0.61, and fluconazole 17.91 +/- 3.67 microg/mL. CONCLUSION Our study supports that azoles could be used as first-line treatment, as oxiconazole is very effective for both dermatophytes and C. albicans. Correlation between in vitro results and clinical outcomes of cases of dermatophytes is still to be established and interpretive breakpoints defined, in order to increase the quality of patient care in tinea pedis.

A spectrophotometric method is described for the determination of oxiconazole in raw material and in topical lotion. This method is based on the reaction of the oxiconazole with methyl orange in buffered aqueous solution of citric acid at pH 2.3. The chromogen, being extractable with dichloromethane, could be measured quantitatively with maximum absorption at 427 nm. The Lambert-Beer law was obeyed in the concentration range of 4.0-14.0 microg ml(-1). A prospective validation of the method showed that the method was linear (r=0.9995), precise (intra-day: CV=1.57% and inter-day: CV=1.50%) and accurate (mean recoveries: 99.69%). The results compared favourably with those of the HPLC method.

A total of 56 strains belonging to 4 species of dermatophytes were tested against 10 antifungal drugs by using a modification of the NCCLS (M38-P) standard for filamentous fungi. The minimum inhibitory concentration (MIC) values obtained using the dilution method were compared with the diameters of growth inhibition zones using the disk diffusion method. The antifungals used were itraconazole, fluconazole, ketoconazole, miconazole, sulconazole, oxiconazole, bifonazole, griseofulvin, ciclopiroxolamine, and terbinafine. Relative to the other agents tested. terbinafine possessed the highest antifungal activity against all of the dermatophytes. In contrast, fluconazole was the least active drug. An increase of MIC values was accompanied by a decrease of growth inhibition zone diameter. The disk diffusion method of fungal susceptibility assessment yields data consistent with results obtained front the dilution method. The Study suggests the potential value of the disk diffusion method as a convenient alternative method for testing the susceptibilities of dermatophytes. (C) 2004 Elsevier Inc. All rights reserved.

Some new oxime ethers of types 7 and 8, in which the methyleneaminoxy group, C=N-O, of oxiconazole 6 is in an inverted atomic sequence, were synthesized and tested for their antifungal activities. Among them, the type 7 compounds, such as the N-ethoxy-morpholino-substituted derivatives 7l-o (Table 1), showed good antifungal properties against the Candida strains tested, with minimum inhibitory concentration (MIC) values similar to those of the reference drug 6. A remarkable result was obtained with these types of azoles, which had shown a cidal character against Candida albicans, while the reference drug oxiconazole was only fungistatic in the same tests. This fact may be seen from a comparison of the MIC values with those of the minimum fungicidal concentration (MFC) values for most of the type 7 compounds assayed that have shown differences between the MIC and the MFC, which are lower than three double diluitions. A simple molecular modeling of the P450 14-alpha-sterol demethylase from C. albicans (Candida P450DM) was built in order to understand how the structural differences between type 7 compounds and oxiconazole 6 can induce different antifungal profiles. The results of this work seem to confirm that it is possible to reverse the atomic sequence of the methyleneaminoxy group, C=N-O, of 6, obtaining new imidazoles possessing good antifungal properties.

UNLABELLED Terbinafine is an allylamine antifungal agent which has fungicidal activity against a wide variety of dermatophytes, moulds and certain dimorphic fungi, and fungistatic activity against Candida albicans. Oral terbinafine 250 mg/day is effective in the treatment of superficial dermatophyte infections such as onychomycosis, tinea pedis and tinea corporis/cruris, generally achieving mycological cure in > 80% of patients. The drug is also effective in children with tinea capitis when administered orally in the dosage range 62.5 to 250 mg/day for 4 weeks. Comparative data indicate that oral terbinafine is more effective than continuous or intermittent intraconazole in dermatophyte onychomycosis, and is as effective as itraconazole 400 mg/day in tinea pedis. The drug has shown greater efficacy than griseofulvin in dermatophyte onychomycosis, tinea pedis and tinea corporis/cruris, and comparable efficacy in children with tinea capitis. Additionally, oral terbinafine is more effective than ketoconazole 200 mg/day in tinea corporis/cruris. Topical terbinafine 1% formulations are effective when applied once or twice daily for up to 2 weeks, achieving mycological cure in > 80% of patients with tinea pedis, tinea corporis/cruris, cutaneous candidiasis and pityriasis versicolor. Its formulations are at least as effective as miconazole 2% cream and naftifine 1% gel in tinea pedis, and more effective than clotrimazole 1% cream, bifonazole 1% cream and oxiconazole 1% lotion. Mycological cure rates achieved with terbinafine generally improve after treatment cessation, reflecting the drug's fungicidal mechanism of action and its residual effect in tissue. Terbinafine is well tolerated after oral or topical administration and has a relatively low potential for drug interactions. Pharmacoeconomic data support the use of terbinafine in dermatophyte infections of the skin or nails. CONCLUSIONS Evidence suggests that oral terbinafine is the treatment of choice for dermatophyte onychomycosis, as it achieves high rates of mycological and clinical cure, is generally well tolerated and has a relatively low potential for drug interactions. It must also be considered a first-line treatment option, along with itraconazole, in cutaneous mycoses which warrant systemic treatment; topical terbinafine is a treatment of choice in less extensive mycoses. The use of terbinafine in non-dermatophyte or mixed infections has not been fully defined.

The synthesis of a new series of 5-or 6-methyl-2-(2,4-disubstituted phenyl) benzoxazoles (4, 5) is described in order to determine their antimicrobial activities and feasible structure-activity relationships. The synthesized compounds were tested in vitro against three Gram-positive bacteria, three Gram-negative bacteria and the yeast Candida albicans, in comparison with several control drugs. Microbiological results exhibited that the synthesized compounds possess a broad spectrum of antibacterial activity against the tested microorganisms. The compounds 4b and 4c indicated some antibacterial activity against Staphylococcus aureus having a minimum inhibitory concentration (MIC) of 12.5 micrograms/ml. Moreover, the compound 5a revealed a significant antibacterial activity against the enterobacter Pseudomonas aeruginosa showing a MIC value of 25 micrograms/ml, i.e. more potent than the control drugs tetracycline and streptomycin. For the antimycotic activity against the yeast C. albicans, the derivative 4c was found to be more active than the other synthesized compounds with a MIC value of 12.5 micrograms/ml, but one-fold less potent than the control drugs oxiconazole and haloprogin.

Poor response of fungal nail infections to topical treatment with antimycotics is probably related to poor drug penetration into the infected nail. The aim of the present study was to evaluate the in vivo nail penetration of the antimycotic oxiconazole from a 1% w/v lotion, and to evaluate the potential penetration enhancing properties of co-delivered acetylcysteine. Six healthy volunteers were treated with 1% w/v oxiconazole lotions with or without acetylcysteine (15% w/v), according to a left–right study design. Treatment was performed twice daily for 6 weeks. Nail clippings were collected every 2 weeks over an 8-week period, until 2 weeks after the treatment stopped. Oxiconazole levels at various depths in sectioned nail clippings were measured by gas chromatographic analysis of ethanolic nail extracts. Topical treatment with oxiconazole nitrate without acetylcysteine resulted in maximum drug levels in the upper 0–50-μm layers varying between 120 and 1420 ng mg−1; levels decreased downwards. Total uptake into the nail was less than 0.2% of the topical dose, indicating a substantial barrier function of the nail. Co-delivery with acetylcysteine statistically significantly prolonged the mean residence time of oxiconazole in the upper 51–100-μm ring finger nail layers from 3.7–4.9 weeks to 4.1–6.4 weeks, implying increased retention of the drug in the nail. Mean (±S.D.) peak drug levels increased from 790±420 ng mg−1 to 1570±820 ng ml−1 in the upper 0–50-μm layer, which suggested a variably enhancing effect of acetylcysteine on the extent of oxiconazole nail penetration in the upper nail layers. The effect of acetylcysteine was speculated to be related to increased binding of oxiconazole to nail constituents.

Six new polyazole derivatives from 2-(2,4-dichlorophenyl)-1,3-dioxolane were studied for their antifungal activity against pathogenic fungi for humans and animals. The antimycotic effect was largely restricted to the filamentous fungi with Aspergillus fumigatus and Scedosporium apiospermum being remarkably susceptible. Three compounds were as effective as the two references, ketoconazole and oxiconazole. The structure-activity relationships revealed that an ‘oxime group’ combined with four chlorine atoms increased the antifungal properties of the chemical series.

Antecedentes: Los hongos dermatofitos se agrupan en geofílicos (suelo), zoofílicos (animales) y antropofílicos (humanos), dependiendo de la fuente de queratina que pueden utilizar como sustrato nutritivo energético. Objetivos: Se ha estudiado la sensibilidad in vitro de aislamientos clínicos de hongos dermatofitos pertenecientes a los 3 grupos ecológicos frente a antifúngicos utilizados para el tratamiento tópico de las dermatofitosis, con el fin de conocer la influencia del grupo en esta actividad. Métodos: Mediante un micrométodo de dilución en medio líquido se determinó la actividad antifúngica in vitro de 9 antifúngicos de uso tópico: amorolfina (AMR), bifonazol (BFZ), clotrimazol, econazol, ketoconazol, miconazol, oxiconazol, terbinafina (TRB) y tioconazol frente a 124 aislamientos clínicos de hongos dermatofitos pertenecientes a los 3 grupos ecológicos (antropofílicos, zoofílicos y geofílicos). Resultados: La actividad antifúngica in vitro mostró diferencias según el grupo ecológico en el que se dividen los hongos dermatofitos, observándose también un patrón especie dependiente. Conclusiones: Los derivados azólicos mostraron un patrón de actividad similar entre ellos, con mayor actividad frente a los antropofílicos > zoofílicos > geofílicos. La actividad de TRB y AMR, por el contrario, fue: zoofílicos > antropofílicos > geofílicos. TRB y AMR fueron las más activas frente a los 3 grupos y BFZ la menos activa. Background: Dermatophytes can be divided into geophilic (soil), zoophilic (animals) and anthropophilic (humans) strains, depending on the source of the keratin that they use for nutritional purposes. Aims: The in vitro susceptibility of clinical isolates of dermatophyte fungi has been studied in the 3 ecological groups with several antifungal agents for the topical management of dermatophytoses in order to determine their relationship with the ecological group. Methods: A standardised dilution micromethod in a liquid medium was used for the determination of the in vitro antifungal activity of 9 topical antifungal drugs: amorolfine (AMR), bifonazole (BFZ), clotrimazole, econazole, ketoconazole, miconazole, oxiconazole, terbinafine (TRB) and tioconazole. The in vitro activity was obtained against 124 clinical isolates of dermatophyte moulds from the anthropophilic, zoophilic and geophilic ecological groups. Results: The in vitro antifungal activity was different depending on the ecological group, although a species-dependent profile was also observed. Fil: Carrillo Muñoz, Alfonso Javier . ACIAM. Departamento de Microbiología; España Fil: Tur Tur, Cristina. Centre d’Atenció Primària Manso; España Fil: Cárdenes, Delia. ACIAM. Departamento de Microbiología; España Fil: Rojas, Florencia Dinorah. Universidad Nacional del Nordeste. Instituto de Medicina Regional; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Nordeste; Argentina Fil: Giusiano, Gustavo Emilio. Universidad Nacional del Nordeste. Instituto de Medicina Regional; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Nordeste; Argentina

CME Educational Objectives 1. Identify the clinical presentation of granuloma annulare. 2. Describe the differential diagnosis for granuloma annulare. 3. Discuss the appropriate management for granuloma annulare. A 12-year-old healthy male presented to the dermatology clinic for evaluation of lesions on his feet. The lesions were bilateral and had been present for at least 6 months. Multiple topical treatments had been prescribed in the past, including miconazole nitrate 2% cream, oxiconazole 1% cream and alclometasone dipropionate 0.05% ointment. Each had been used for several weeks without improvement. Because of this, the referring doctor prescribed griseofulvin microsize 250 mg twice daily for 4 weeks and referred the patient to dermatology. The patient denied pruritus or pain. Review of systems, medical history, and family history were unremarkable.

PubMedID: 23482479 Objective. The aim of this study is to evaluate the ototoxicity of topical oxiconazole and boric acid in alcohol solutions. Study Design. Prospective controlled animal study. Setting. Research laboratory. Method. Fifty adult Wistar albino rats were divided into 5 groups consisting of 10 animals each. The right tympanic membranes were perforated, and baseline and posttreatment distortion product otoacoustic emission (DPOAE) measurements were performed. Results. The solutions were applied through the external ear canal to the middle ear twice a day for 14 days. The rats in group I and group II received 0.1 mL of oxiconazole-containing solution drops and 4% boric acid in alcohol solution drops, respectively. Group III received gentamicin solution (40 mg/mL) (ototoxic control), group IV received saline solution, and group V was followed without any medication. The baseline DPOAE results of the right ears of all animals tested were normal. Animals in groups I, II, IV, and V showed no statistically significant change in the DPOAE amplitudes. The rats in the gentamicin group showed a significant decrease. Conclusion. This study demonstrates that topically used oxiconazole and boric acid in alcohol solutions to the middle ear appear to be safe on the inner ear of rats. The safety of these drugs has not yet been confirmed in humans. Caution should be taken when prescribing these drugs, especially to patients who had tympanic membrane perforation. Ear drops should be chosen more carefully in an external ear infection for patients with tympanic membrane perforation to avoid ototoxicity.© American Academy of Otolaryngology-Head and Neck Surgery Foundation 2013. Firat University Scientific Research Projects Management Unit Competing interests: None. Sponsorships: None. Funding source: Çukurova University Scientific Research Project Fund. We thank Gülşah Seydaoğlu, MD, for her help on statistical analysis. Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article. This article was presented as a poster at the 2012 AAO-HNSF Annual Meeting & OTO EXPO; September 9-12, 2012; Washington, DC.

Objective: Topical preparations are widely used in the treatment of infections of the external auditory canal and middle ear. However, they can pass through the round window and effect the inner ear. The aim of this study is to evaluate the ototoxicity of topical oxiconazole and boric acid in alcohol solutions.Method: Five groups of 10 male Wistar albino rats. The right tympanic membranes of all of the rats were perforated and baseline and posttreatment distortion product otoacoustic emission (DPAOE) measurements were performed. Oxiconazole, boric acid in alcohol, salin, and gentamicin solutions were applied to the right external ears.Results: The solutions were applied through the external ear canal to the middle ear twice a day for 15 days. The rats in group I and group II received oxiconazole and boric acid in alcohol solutions, respectively. Group III received gentamicin (ototoxic control), group IV received saline solution, and group V was followed without any medication. The baseline DPOAE results o...

A 1% cream formulation of oxiconazole, an imidazole derivative, was used to treat 50 cases of tropical dermatomycoses, including 30 cases of pityriasis versicolor, 9 of tinea pedis (3 each due to Trichophyton rubrum, Trichophyton mentagrophytes, and Epidermophyton floccosum), 5 each of tinea corporis and tinea cruris all caused by T rubrum, and one of foot and groin infection due to Trichosporon cutaneum. In most cases, oxiconazole produced a clinical and mycologic cure within 2 to 4 weeks of initiating treatment; very few relapses occurred. The drug was well tolerated, and no side effects were reported. Oxiconazole is recommended as an effective therapy for superficial fungal infections of the skin.