Luliconazole

Absorption

Although luliconazole is administered topically, clinical studies have shown that after the first dose in patients with tina pedis, a maximum plasma concentration of 0.40 ± 0.76 ng/mL (mean ± SD) occurred in 16.9 ± 9.39 hours (mean ± SD).

Toxicity

In clinical trials, no serious toxicity was reported, only local irritation (mild contact dermatitis and cellulitis) at the site of application was found.

Description

Luliconazole is a member of the imidazole class of antifungal agents, with specific utility as a dermatological antimycotic drug. It was launched in Japan as a topical agent for the treatment of athlete’s foot. Luliconazole is an optically active drug with (R)-configuration at its chiral center. It is structurally related to lanoconazole, which has been marketed as a racemic mixture since 1994. As with other azole antifungal drugs, the mechanism of action of luliconazole is the inhibition of sterol 14-a-demethylase, and subsequently, inhibition of ergosterol biosynthesis. The in vivo activity of luliconazole against dermatophytes has been evaluated in the guinea pig model of tinea pedis. In this study, a 1% topical solution of luliconazole, administered once daily for seven days, achieved complete mycologic cure. Additionally, there were no occurrences of relapse for up to 16 weeks after the treatment. No data is currently available on the clinical efficacy of luliconazole. The chemical synthesis of luliconazole involves the condensation of 1-(cyanomethyl)imidazole with carbon disulfide to produce a dithioate intermediate, and subsequent alkylation with either the mesylate derivative of (S′)-1-(2,4-dichlorophenyl)-2-bromoethanol or the bis-mesylate derivative of (S′)-1-(2,4-dichlorophenyl)ethane-1,2-diol. .

Originator

Nihon Nohyaku (Japan)

The Uses of Luliconazole

Luliconazole is an azole antifungal drug. It was approved by the FDA (USA) in November 2013 and is marketed under the brand name Luzu. Luliconazole is also approved in Japan.

Indications

Luliconazole is indicated for the treatment of interdigital tinea pedis, tinea cruris, or tinea corporis infections caused by Trichophyton rubrum and Epidermophyton floccosum.

Background

Luliconazole is a topical antifungal agent that acts by unknown mechanisms but is postulated to involve altering the synthesis of fungi cell membranes. It was approved by the FDA (USA) in November 2013 and is marketed under the brand name Luzu. Luliconazole is also approved in Japan.

Definition

ChEBI: Luliconazole is a dichlorobenzene.

brand name

Lulicon

Pharmacokinetics

Luliconazole kills the organisms Trichophyton rubrum and Epidermophyton floccosum, most likely by altering their fungal cell membranes.

Synthesis

Synthesis of luliconazole started with diol 77, prepared according to literature procedure in 98%ee which was activated by converting to dimesylate 78 in 99% yield and coupled to dipotassium enolate 80, prepared in situ by reacting cyano methylimidazole 79 with carbon disulfide, to give luliconazole (XI), 99% ee in 48% yield.

Metabolism

The metabolism of luliconazole has yet to be determined.

Mode of action

The mechanism of action of luliconazole is as a Cytochrome P450 2C19 Inhibitor.