Disease relevance of Amorolfine

• In addition to known kex2 phenotypes, such as pH and calcium hypersensitivity, the mutants grew in cellular aggregates and were found to be hypersensitive to several antifungal drugs that target the cell membrane, including azoles, amorolfine and amphotericin B [1].
• At present, the major potential indication for topical amorolfine appears to be onychomycosis [2].
• Overall cure and improvement was observed in approximately 85 to 90% of patients with superficial dermatomycoses following treatment with amorolfine 0.25% cream for up to 6 weeks [2].
• The results with C. albicans and amorolfine and terbinafine accord with their known in vivo efficacy in mycoses involving low-temperature superficial sites and poor activity against mycoses involving deep body sites [3].
• Allergic contact dermatitis from amorolfine cream [4].

High impact information on Amorolfine

• When C. albicans-infected living skin equivalent was exposed to amorolfine, amplicons of ACT1 and SAP2 mRNA were not detected in total RNA extracts [5].
• Interestingly, the morpholine amorolfine also displayed a weak but significant effect (IC50, 30 microM) [6].
• 5-Fluorocytosine promoted incorporation of radioactivity into 4-desmethylsterols (P < 0.01), and enhanced the relative and absolute increases of ergosterol (P < 0.05) in C. glabrata incubated aerobically with an SBI (miconazole or amorolfine) [7].
• OBJECTIVE: In an open, randomized, clinical study of toenail onychomycosis with matrix area involvement, two alternative regimens of topical amorolfine/oral itraconazole therapy were compared with itraconazole monotherapy [8].
• Analysis of the computer records of 100 general practices from the CompuFile Doctors Independent Network revealed 1492 patients receiving treatment for onychomycosis in the first 6 months of 1994 with terbinafine, tioconazole, amorolfine or griseofulvin [9].

Chemical compound and disease context of Amorolfine

• In our opinion, the addition of amorolfine to oral itraconazole pulse therapy is of value in the treatment of moderate to severe Candida fingernail onychomycosis [10].
• The management of onychomycosis using topical agents has improved with the introduction of ciclopirox and amorolfine nail lacquers; other topical agents may be less effective [11].
• A clinical double-blind trial comparing amorolfine cream 0.5% (RO-14-4767) with bifonazole cream 1% in the treatment of dermatomycoses [12].
• METHODS: The minimum inhibitory concentrations (MIC(80)) were recorded for pathogens that are most frequently responsible for onychomycosis against combinations of several antifungal agents, namely, fluconazole, itraconazole, terbinafine and amorolfine [13].
• MATERIALS AND METHODS: A varnish containing 5% amorolfine was applied once or twice a week for 6 months in six patients affected by nystatin-resistant denture-related stomatitis [14].

Biological context of Amorolfine

• Present data suggest that mean percutaneous absorption of amorolfine following topical application of the 0.25% cream formulation should not exceed 8-10% of the dose applied [15].
• At 0.2, 2 and 5 micrograms/ml amorolfine did not have any significant inhibitory or enhancing effect on phagocytosis whether following simultaneous addition of blastospores and drug to the neutrophils, prior treatment of neutrophils for 2 h before addition of blastospores or prior treatment of blastospores for 2 h [16].
• Kinetics of amorolfine in human nails [17].

Anatomical context of Amorolfine

• OBJECTIVE: This open randomized study examined the efficacy of a combination of oral terbinafine and topical amorolfine in the treatment of severe dermatophyte toenail onychomycosis with matrix area involvement [18].
• Cytoplasmic membranes and other membranous structures of organelles such as nuclei and mitochondria were disrupted or fused, thereby losing their essential physiological activity in hyphal cells pretreated with 80 ng/ml of amorolfine [19].
• TEM revealed thickening of the cell walls and the accumulation of electron-dense granular structures in both the wall and cytoplasm in thin-sectioned cells pretreated with 8 ng/ml or more of amorolfine, although the nuclear and mitochondrial architecture was not noticeably influenced [19].

Associations of Amorolfine with other chemical compounds

• Accordingly, amorolfine, ciclopirox, econazole and naftifine are expected to be especially effective against dermatophytes, whereas in the case of an infection with yeasts only, amorolfine and ciclopirox are promising [20].
• It was demonstrated that at 24 h after product application, remanence of amorolfine nail lacquer on the thumbnails was significantly higher than that of ciclopirox (p < 0.05) and that of tioconazole on the thumb- and toenails at each time point up to 8 h after product application (all p < 0.05) [21].
• Oxiconazole with a minimum inhibitory concentration of 0.1 micrograms/ml-1 after 72 h and amorolfine at a concentration of 0.001 micrograms/ml-1 after 72 h were the most active ones against S. pruinosum and C. oxysporum respectively [22].
• In BFZ-treated cultures, similar morphological changes were seen in the hyphae of T. mentagrophytes, but these changes were milder than observed in the AMF-treated samples, and actin gene fragments were amplified in all of these samples [23].
• Effect of oxiconazole and Ro 14-4767/002 on sterol pattern in Candida albicans [24].

Analytical, diagnostic and therapeutic context of Amorolfine

• In clinical trials, application of amorolfine 5% nail lacquer once or twice weekly for up to 6 months produced mycological and clinical cure in approximately 40 to 55% of patients with mild onychomycosis 3 months after cessation of therapy [2].
• The minimum inhibitory concentration (MIC) of amorolfine against dermatophytes ranged from 0.01 to 0.08 microg ml(-1) [25].
• This study examined the effects of the antifungal agents amorolfine hydrochloride (AMF) and bifonazole (BFZ) on actin mRNA expression determined by reverse transcription-polymerase chain reaction (RT-PCR) amplification, and the morphology of Trichophyton mentagrophytes [23].

References