Clotrimazole - How It Works
Clinical pharmacology details from the US FDA-approved label: how Clotrimazole works in your body, how it's absorbed, how long it stays active, and how it's eliminated.
Mechanism of Action
12.1 Mechanism of Action Clotrimazole is an azole antifungal [see Clinical Pharmacology ] . Betamethasone dipropionate is a corticosteroid. Corticosteroids play a role in cellular signaling, immune function, inflammation, and protein regulation; however, the precise mechanism of action for the treatment of tinea pedis, tinea cruris and tinea corporis is unknown.
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Clotrimazole is an azole antifungal [see Clinical Pharmacology ] .
Betamethasone dipropionate is a corticosteroid.
Corticosteroids play a role in cellular signaling, immune function, inflammation, and protein regulation; however, the precise mechanism of action for the treatment of tinea pedis, tinea cruris and tinea corporis is unknown.
12.2 Pharmacodynamics Vasoconstrictor Assay : Studies performed with clotrimazole and betamethasone dipropionate cream indicate that these topical combination antifungal/corticosteroids may have vasoconstrictor potencies in a range that is comparable to high-potency topical corticosteroids.
However, similar blanching scores do not necessarily imply therapeutic equivalence.
12.3 Pharmacokinetics Skin penetration and systemic absorption of clotrimazole and betamethasone dipropionate following topical application of clotrimazole and betamethasone dipropionate cream has not been studied.
The extent of percutaneous absorption of topical corticosteroids is determined by many factors, including the vehicle, the integrity of the epidermal barrier, and the use of occlusive dressings.
Topical corticosteroids can be absorbed from normal intact skin.
Inflammation and/or other disease processes in the skin may increase percutaneous absorption of topical corticosteroids.
Occlusive dressings substantially increase the percutaneous absorption of topical corticosteroids [see Dosage and Administration ] .
Once absorbed through the skin, the pharmacokinetics of topical corticosteroids are similar to systemically administered corticosteroids.
Corticosteroids are bound to plasma proteins in varying degrees.
Corticosteroids are metabolized primarily in the liver and are then excreted by the kidneys.
Some of the topical corticosteroids and their metabolites are also excreted into the bile.
12.4 Microbiology Mechanism of Action : Clotrimazole, an azole antifungal agent, inhibits 14-α-demethylation of lanosterol in fungi by binding to one of the cytochrome P-450 enzymes.
This leads to the accumulation of 14-α-methylsterols and reduced concentrations of ergosterol, a sterol essential for a normal fungal cytoplasmic membrane.
The methylsterols may affect the electron transport system, thereby inhibiting growth of fungi.
Activity In Vitro and In Vivo : Clotrimazole has been shown to be active against most strains of the following dermatophytes, both in vitro and in clinical infections, Epidermophyton floccosum , Trichophyton mentagrophytes , and Trichophyton rubrum [see ] .
Drug Resistance : Strains of dermatophytes having a natural resistance to clotrimazole have not been reported.
Resistance to azoles, including clotrimazole, has been reported in some Candida species.
Pharmacokinetics
12.3 Pharmacokinetics Skin penetration and systemic absorption of clotrimazole and betamethasone dipropionate following topical application of clotrimazole and betamethasone dipropionate cream has not been studied. The extent of percutaneous absorption of topical corticosteroids is determined by many factors, including the vehicle, the integrity of the epidermal barrier, and the use of occlusive dressings. Topical corticosteroids can be absorbed from normal intact skin. Inflammation and/or other disease processes in the skin may increase percutaneous absorption of topical corticosteroids. Occlusive dressings substantially increase the percutaneous absorption of topical corticosteroids [see Dosage and Administration ] . Once absorbed through the skin, the pharmacokinetics of topical corticosteroids are similar to systemically administered corticosteroids. Corticosteroids are bound to plasma proteins in varying degrees. Corticosteroids are metabolized primarily in the liver and are then excreted by the kidneys. Some of the topical corticosteroids and their metabolites are also excreted into the bile.