Roques C¹, Jeanjean M², Ermosilla V², Sibaud V, Panizzutti C¹

¹Laboratory of Industrial Microbiology and Fonderephar – UFR of Pharmaceutical Sciences – 35, chemin des Maraîchers – 31062 Toulouse cedex 4 ²Pierre Fabre Research Institute – allée camille Soula, Vigoulet-Auzil- 31 322 Castanet Tolosan cedex- France

The hydroxy-pyridones (ciclopirox and ciclopiroxolamine) have an antifungal activity that is original in terms of its mode of action and its spectrum. The molecules act on various targets of the fungal cell, leading to inhibition of the growth of dermatophytes, yeasts and moulds. This growth inhibiting activity is associated with a true fungicidal action which marks one of the basic differences between the hydroxy-pyridones and the azoles. The aim of the present work was to define the fungicidal activity of ciclopiroxolamine in vitro against Malassezia species, according to the concentration. The interaction of ciclopiroxolamine with pyrithione zinc (association present in Kelual DS shampoo) was also studied.

Assays were performed according to the European Standard for Antiseptics and Disinfectants, for contact times between ciclopiroxolamine (associated or not to pyrithione Zn) and yeasts ranging from 5 to 30 minutes. The end of the contact time was validated using a filtration method. Testing strains were Malassezia restricta IP 2392.96 and Malassezia globosa IP 2387.96 which represent the main Malassezia species implicated in seborrheic dermatitis. Ciclopiroxolamine solutions were tested at 1%, 1.5% and 2%. The association of 1.5% ciclopiroxolamine with 1% pyrithione Zn was also tested in the same conditions.

A five minute contact time with the two strains led to a rapid decrease of the inoculum ranging from 0.4 log (1% ciclopiroxolamine) to 0.7 log (2% ciclopiroxolamine). The log reduction significantly increases with the contact time. After 15 minutes of contact between ciclopiroxolamine solutions and Malassezia strains, we observed about 1 log reduction for the 1% ciclopiroxolamine solution and above 2 log for the 1.5% and 2% ciclopiroxolamine solutions. No significant difference was noted between the two tested strains. The association of 1.5% ciclopiroxolamine to 1% pyrithione Zn is characterized by an indifferent or positive interaction, especially for the short contact times. No antagonism was observed for any strains or any contact times.

In conclusion, this study clearly demonstrates the in vitro fungicidal efficiency of ciclopiroxolamine against Malassezia species. On the other hand, we have demonstrated that the association of ciclopiroxolamine with pyrithione zinc does not present an antagonistic effect and that pyrithione zinc improves the fungicidal efficacy of ciclopiroxolamine against some Malassezia species.

These results underline the potent interest of this association in the treatment of seborrheic dermatitis.