Indications
Clotrimazole is utilized for both topical and oral applications, catering to a variety of fungal infections. Topically, clotrimazole cream is prescribed for the treatment of dermal infections such as tinea pedis, tinea cruris, and tinea corporis, predominantly caused by Trichophyton rubrum, Trichophyton mentagrophytes, and Epidermophyton floccosum. It is also effective against candidiasis due to Candida albicans, tinea versicolor caused by Malassezia furfur, and diaper rash infected by Candida albicans. In certain formulations, clotrimazole is combined with betamethasone dipropionate, a corticosteroid. For oral treatments, clotrimazole troches are indicated for managing oropharyngeal candidiasis and serve as a prophylactic measure to decrease the occurrence of this condition in immunocompromised patients, such as those undergoing chemotherapy, radiotherapy, or steroid therapy for leukemia, solid tumors, or renal transplantation. However, it should be noted that troches are not indicated for systemic mycoses.
Pharmacodynamics
Clotrimazole functions as a broad-spectrum antifungal agent, primarily exerting a fungistatic effect by altering the cell membrane permeability of yeasts, thereby inhibiting their growth. At lower concentrations, up to 20 mcg/mL, clotrimazole exhibits a fungistatic action, while at higher concentrations, it demonstrates fungicidal activities against Candida albicans and other Candida species in vitro. Despite once being rare, resistance to clotrimazole has become more prevalent in various patient populations. Although primarily classified as fungistatic, clotrimazole does exhibit fungicidal properties under specific circumstances.
Absorption
Clotrimazole is characterized by minimal systemic absorption, which significantly mitigates potential drug interactions during its use. This limited absorption underscores its efficacy and safety profile for both topical and localized oral treatments.
Metabolism
Clotrimazole undergoes hepatic metabolism, where it is converted into inactive metabolites.
Mechanism of Action
Clotrimazole functions primarily by compromising the integrity of the fungal cell membrane, specifically by inhibiting the biosynthesis of ergosterol, a vital component of these membranes. This inhibition impairs the cell's ability to maintain an intact and functional membrane, as ergosterol not only forms a structural basis but also promotes fungal growth in a hormone-like manner. Consequently, when ergosterol synthesis is obstructed, fungal growth is inhibited in a dose-dependent manner. Although the reduction in ergosterol, resulting from the inhibition of lanosterol 14-demethylase (CYP51), is the chief mechanism behind clotrimazole's antifungal efficacy, the compound also exhibits additional pharmacological actions. These include inhibiting sarcoplasmic reticulum Ca2+-ATPase, depleting intracellular calcium, and preventing calcium-dependent potassium and voltage-dependent calcium channel activity. These actions account for clotrimazole's various effects beyond its antifungal properties.
