Ciclopiroxolamine (Loprox) was the first representative of hydroxpyridones to be developed as a topical antifungal. In the microtitration test and in a skin model using excised skin prices of slaughtered pigs, the fungistatic and fungicidal activity as well as the penetration kinetics of ciclopiroxolamine and ciclopirox were compared with those of the azole compounds bifonazole, clotrimazole, econazole, miconazole, oxiconazole, and tioconazole, and with other antimycotics such as naftifine, sulbentine, tolciclate, and tolnaftate. Clotrimazole had an in vitro inhibitory activity superior to that of the hydroxypyridone ciclopiroxolamine; the latter compound, however, exhibited faster penetration and higher inhibitory or fungicidal activity than the azoles and other antimycotics in the pig skin model. Studies of cream formulations with antimycotics at the bottom layer of the stratum corneum (close to the stratum granulosum) showed that ciclopiroxolamine cream had the most prominent inhibitory effect (93%) and the highest fungicidal activity (98%). The other antimycotics tested exhibited growth inhibition rates of 50% or less and lower fungicidal rates. Inoculated pig skin was treated with lacquer formulations to show that ciclopirox completely inhibited the growth of Trichophyton mentagrophytes, whereas the clotrimazole-treated samples allowed only 0.47% growth. The fungicidal activity of lacquer formulations was 99% for ciclopirox and around 90% for most of the azoles on the pig skin model. The necessity of models tackling the complex penetration kinetics in human skin was discussed.

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 Gewebeaktivitätstest mit direkter Inokulation (D‐GAT) wurde mit Handelspräparaten der Nichtazol‐Antimykotika Ciclopiroxolamin, Tolnaftat und Naftifin in verschiedenen Hornschichtniveaus eine höhere Hemmaktivität gegenüber Trichophyton mentagrophytes (Standard‐Stamm) erzielt als mit solchen der Azol‐Antimykotika Econazol, Miconazol, Clotrimazol, Oxiconazol und Bifonazol. Rasch trocknende Lösungen von Antimykotika ergaben durchweg höhere Hemmaktivitäten als Cremes. Im Ultrafiltrations‐Gewebeaktivitätstest (UFT‐GAT) gegenüber Candida albicans (2 Stämme) ergab sich nach erzielter Wirksamkeit die Rangfolge Ciclopiroxolamine – Mehrzahl der Azolantimykotika – Bifonazol und Naftifin. 2. In Fungizidie‐Testen gegenüber T. mentagrophytes (2 Stämme) und Microsporum gypseum (1 Stamm) wurde zunächs...

Summary: The biogenous amines methylamine, dimethylamine, ethylamine, ethanol‐amine, piperidine, β‐phenylethylamine, serotonine, pyridoxamine, hordenine, ammonia, isoamylamine, spermine and spermidine were qualitatively detected, and dimethylamine, ethanolamine, piperidine, β‐phenylethylamine, serotonine and pyridoxamine and hodenine were quantitatively determined using two‐dimensional thin‐layer chromatography in Trichophyton mentagrophytes, Trichophyton rubrum, Microsporum canis and Candida albicans treated with DANS, according to Seiler and Wiechmann's method. However, no methylamine was detected in Microsporum canis and no ethylamine in Candida albicans. The presence of a certain amine was established on the strength of identity of reference values, of colour spots and knowledge of the chemical transformation undergone. For quantitative analysis, the spectro‐fluorometric reading of the DANS amide extracted from the silica‐gel was used. The amine content varied between 10‐8 and 10‐11 moles per gram of fungus‐culture for each amine and fungus‐culture investigated. For each amine, the quantitiy present lay within a range of a power of ten. Only serotonine in Candida albicans was a power of ten higher than the rest. Histamine could not be detected. To confirm these results, the presence of serotonine, ethanolamine and piperidine in Candida albicans and the absence of histamine were investigated by identifying the amines as their t‐dimethylamino‐naphthaline‐5‐sulphonyl derivatives using‐mass‐spec‐troscopy. The results confirmed the thin‐layer chromatography results. Again, no histamine was detected. Zusammenfassung: Die biogenen Amine Methylamin, Dimethylamin, Äthylamin, Äthanolamin, Properdin, β‐Phenäthylamin, Serotonin, Pyridoxamin, Hordenin, Ammoniak, Isoamylamin, Spermin und Spermidin wurden qualitativ, Dimethylamin, Äthanolamin, Piperdin, β‐Phenäthylamin, Serotonin, Pyridoxamin und Hordenin quantitativ mittels zweidimensionaler Dünnschichtchromatographie nach Umsetzung mit 1‐Dimethylamino‐naphthalin‐5‐sulfonyl nach der Methode Seiler und Wiechmann inin Trichophyton mentagrophytes, Trichophyton rubrum, Microsporum canis und Candida albicans – mit Ausnahme von Methylamin bei Microsporum canis und Äthylamin bei Candida albicans – nachgewiesen. Identität der Rf‐Werte, Fluorescenzfarbe und der Weg der Aufbereitung lassen die Annahme des Vorkommens der ge‐nannten Amine zu. Zur quantitativen Analyse wurde die spektro‐fluorimetrische Messung der aus Kiesel‐gel eluierten DANS‐Amide verwandt. Der Amingehalt bewegte sich zwischen 10‐8 bis 10‐11 Mol pro 1 Gramm Pilzkultur je nach Amin und untersuchter Pilzkultur. Der jeweilige Amingehalt lag bei den vier Pilzkulturen innerhalb einer Zehner‐potenz; lediglich Serotonin war bei Candida albicans um eine Zehnerpotens höher. Histamin konnte nicht nachgewiesen werden. Um diese Ergebnisse zu sichern wurde das Vorhandensein von Serotonin, Äthanol‐amin und Piperidin in Candida albicans und das Fehlen von Histamin durch massen‐spektrometrische Identifizierung in Form ihrer DANS‐D...

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Zusammenfassung Unter Verwendung eines M. gypseum‐Stammes lassen sich im Mycelwuchstest auf Agarmedien, denen Untersuchungsfüissigkeit beigemischt ist, Griseofulvin‐Konzentrationen bis zu 0,02 mcg/ml herab gut erfassen. Hiernach können bei 20 % Serumgehalt im Testmedium noch 0,15 meg Griseofulvin/ml unverdünnten Serums nachgewiesen werden. Im Mycelwuchstest lassen sich bei geeigneten Griseofulvin‐Konzentrationen Standardkurven aufstellen, die unter bestimmten Versuchsbedingungen linear verlaufen. Niedrige Griseofulvin‐Konzentrationen sind auch in modifizierten Diffusionsverfahren und auf hitzekoagulierten Serum‐schichten nachweisbar.