SULCONAZOLE

Absorption

A study done on healthy subjects given sulconazole 1% cream over a seven-day period, showed that the total percutaneous absorption of sulconazole after topical administration was 8.71-11.3% of the dose. Another study also done on healthy volunteers given 1 g of sulconazole 1% cream, estimated that about 12% of the dose was absorbed through the skin. In general, topical imidazoles are poorly absorbed (<15%); however, sulconazole may have higher levels of absorption compared to others.

Toxicity

Sulconazole has been shown to be embryotoxic in a study of rats given 125 times the human dose (in mg/kg) and also resulted in prolonged gestation and dystocia. There are no adequate or controlled studies in pregnant women, therefore sulconazole should only be used during pregnancy if potential benefit justifies potential risk to the fetus.

The Uses of SULCONAZOLE

Sulconazole (Exelderm) is a synthetic, sulfur-substituted imidazole that is structurally related to the other imidazole antifungals (ketoconazole, econazole, and miconazole). It is postulated to inhibit 14-α-demethylase for decreased ergosterol synthesis, increased cell membrane permeability, and resultant cell death. It is active against most dermatophytes, yeast, and P. orbiculare. It also displays activity against some aerobic and anaerobic gram-positive bacteria. Sulconazole is a mild inducer of the cytochrome P-450 microsomal enzymes CYP1A1 and CYP2B1 and could theoretically induce the metabolism of other drugs.

Indications

Sulconazole solution 1.0% is indicated for the treatment of tinea cruris and tinea corporis caused by Trichophyton rubrum, Trichophyton mentagrophytes, Epidermophyton floccosum, and Microsporum canis; and for the treatment of tinea versicolor. Effectiveness has not been proven in tinea pedis (athlete’s foot).

Background

Sulconazole, brand name Exelderm, is a broad-spectrum anti-fungal agent available as a topical cream and solution. Sulconazole nitrate, the active ingredient, is an imidazole derivative that inhibits the growth of common pathogenic dermatophytes, making it an effective treatment for tinea cruris and tinea corporis infections. Sulconazole appears to be effective and well-tolerated in the treatment of superficial fungal infections.

Definition

ChEBI: A member of the class of imidazoles that is 1-ethyl-1H-imidazole in which one of the hydrogens of the methyl group is replaced by a (4-chlorobenzyl)sulfanediyl group while a second is replaced by a 2,4-dichlorophenyl group.

Indications

Sulconazole (Exelderm) is a synthetic, sulfur-substituted imidazole that is structurally related to the other imidazole antifungals (ketoconazole, econazole, and miconazole). It is postulated to inhibit 14-α-demethylase for decreased ergosterol synthesis, increased cell membrane permeability, and resultant cell death. It is active against most dermatophytes, yeast, and P. orbiculare. It also displays activity against some aerobic and anaerobic gram-positive bacteria. Sulconazole is a mild inducer of the cytochrome P-450 microsomal enzymes CYP1A1 and CYP2B1 and could theoretically induce the metabolism of other drugs.

Indications

Topical treatment of mycoses of the skin induced or sustained by fungi such as dermatophytes and yeasts.

Pharmacokinetics

Sulconazole is a broad-spectrum antifungal that inhibits the growth of dermatophytes, yeasts and other filamentous and dimorphic fungi. The relative inhibition factor (RIF), a measurement that represents a fixed portion of the antigungal dose-response curve, can be determined to measure the inhibitory activity of antifungal drugs. Against pathogenic yeasts such as dermatophytes and Aspergilli, sulconazole had similar RIF values compared to other imidazoles. In in vitro conditions, the fungicidal potency of sulconazole depends on its concentration and the growth phase of the inoculum cells. Sulconazole has also shown antibacterial properties in vitro, with inhibitory concentrations (MICs) under 12.5 mg/L against several Staphylococcus species, as well as Streptococcus faecalis and several Gram-positive anaerobes.

Side Effects

Local irritations and allergic reactions may occur in rare cases and are mainly due to the galenic formulation.

Synthesis

Sulconazole, 1-[2,4-dichloro-|?-[(4-chlorobenzyl)thio]phenethyl]-imidazole (35.2.9), is an analog of exonazole. It differs in the replacement of the etheral oxygen bridge (which connects the 4-chlorobenzyl part of the molecule with phenethylimidazole) for a thioether bond. The corresponding changes in the synthesis of this drug are the replacement of the hydroxyl group in 1-(2,4-dichlorophenyl)-2-(1-imidazolyl)-ethanol (35.2.6) with a chlorine atom using thionyl chloride, followed by a reaction of the resulting chloride with 4-chlorobenzylmercaptane to make sulconazole.

Metabolism

Not Available

Solubility in organics

1 part in 3,333 (water), 1 part in 100 (ethanol), 1 part in 130 (acetone), 1 part in 333 (chloroform), 1 part in 2000 (dioxan), 1 part in 71 (methanol), 1 part in 286(chloromethane), 1 part in 10 (pyridine), 1 part in 2000 (toluene).