Dermatopharmacology of ciclopirox nail lacquer topical solution 8% in the treatment of onychomycosis

Abstract

Ciclopirox is a synthetic hydroxypyridone antifungal agent. In contrast to the azoles, glucuronidation is the main metabolic pathway of ciclopirox; therefore interactions with drugs metabolized via the cytochrome P450 system are unlikely. Ciclopirox is also distinct from the common systemic agents, which interfere with sterol biosynthesis. In fact, ciclopirox chelates trivalent cations (such as Fe3+), inhibits metal-dependent enzymes that are responsible for degradation of toxic metabolites in the fungal cells, and targets diverse metabolic (eg, respiratory) and energy producing processes in microbial cells. Ciclopirox is a broad spectrum antimicrobial with activity against all the usual dermatophytes as well as yeast and nondermatophyte molds. It has demonstrated activity against gram positive and negative bacteria, including resistant strains of Staphylococcus aureus. Ciclopirox exhibits fungal inhibitory activity (minimum inhibitory concentration < 4 μg/mL for dermatophytes) as well as fungicidal activity; to date resistance to the drug has not been identified. Ciclopirox has been formulated in a nail lacquer delivery system. After evaporation of volatile solvents in the lacquer, the concentration of ciclopirox in the remaining lacquer film reaches approximately 35%, providing a high concentration gradient for penetration into the nail. Radiolabel data demonstrate penetration into infected nails after only 1 application of the lacquer. Ciclopirox nail lacquer is a topical product that provides an active fungicidal agent in a delivery system capable of promoting nail penetration. With repeated applications, the antifungal agent is homogeneously distributed through all layers of the toenail achieving concentrations of ciclopirox in excess of inhibitory and fungicidal concentrations for most pathogens. Although ciclopirox readily penetrates nails, very low levels of ciclopirox are recoverable systemically, even after chronic use. Ciclopirox nail lacquer 8% is a topical product that provides an active fungicidal agent in a delivery system capable of penetrating nails. (J Am Acad Dermatol 2000;43:S57-69.)