Antifungal products, combined with good footcare, are the most effective treatments for persistent Athlete’s Foot.

 

While Lamisil^®AT and Lamisil Once^® have a direct fungus-killing (fungicidal) action most OTC antifungal products are fungistatic, i.e. they only inhibit fungal growth. The imidazoles like ketoconazole or itraconazole belong to this group and they inhibit a cytochrome P-450 enzyme which leads to a disturbed  fungal ergosterol synthesis.  However, this cytochrome enzyme is also important for the mammalian cell metabolism and for the metabolism of drugs.

As fungistatic agents inhibit the growth of fungus, they discourage it from penetrating the stratum corneum and deeper layers of the skin.  It's the stratum corneum itself, however, that must then shed the arrested organisms. The stratum corneum must, therefore, shed at a faster rate than the fungus penetrates. If therapy is inadequate and environmental conditions are right, the fungus can repenetrate the stratum corneum that is free of the antifungal agent and re-establish the infection. So the key to successful treatment with conventional therapy is to keep using the antifungal until all the fungus is shed.

 

Since most topical antifungals are primarily fungistatic, they must be used for two to four weeks (depending on the location of the infection) to eradicate the infection.  A four-week regimen is usually required for tinea pedis, which is a more stubborn infection, while two weeks is often adequate for tinea cruris and tinea corporis.

 

Typically, symptoms improve early in treatment.  That is, the itching goes away before the fungus is eradicated. The risk associated with early relief of symptoms is that patients will discontinue therapy, resulting in a lack of mycological cure and a risk of future symptomatic relapse under the right environmental conditions. Compliance is highest when symptoms (itching, burning, or stinging) are at their worst. Unfortunately, many sufferers stop treatment when symptoms subside.

 

As fungicides, Lamisil^®AT and Lamisil Once^® require much less in the way of patient compliance. Lamisil AT needs only to be applied daily for seven days, while Lamisil Once^®AT needs just one application. This is because they contain the active ingredient terbinafine hydrochloride, which quickly attacks and kills the fungus rather than simply inhibit its growth.

 

Terbinafine hydrochloride does this by inhibiting squalene epoxidase, the enzyme that converts intracellular squalene to the first intermediate in the pathway leading to the synthesis of ergosterol.¹ Ergosterol is an essential component of fungal cell membranes. This leads to a depletion of ergosterol in the fungal cell which is regarded as a secondary mechanism, resulting in fungistatic action. The primary and more important fungicidal activity is due to the fact that squalene accumulates in intracellular droplets which damage the vacuole and cell membranes.²

 

This, in comparison to the azoles, additional fungicidal action of terbinafine is an important factor for the short treatment duration required for clinical efficacy on the one hand and the lack of acquired resistance on the other hand.¹

 

Furthermore, although squalene epoxidase is present in both mammalian and fungal cells, terbinafine is highly selective for the fungal enzyme which does not cause an inhibitory effect on the human mammalian cells; resulting in a lack of side-effects related to its mechanism of action. ³

 

As squalene epoxidase is not a cytochrome P450 enzyme, terbinafine also has little potential for pharmacokinetic interactions with other drugs.⁴