Amorolfine

The Uses of Amorolfine

Amorolfine is a novel antifungal agent used in the treatment of cutaneous fungal disease.

Background

Amorolfine or amorolfin, is a morpholine antifungal drug that inhibits the fungal enzymes D14 reductase and D7-D8 isomerase. This inhibition affects fungal sterol synthesis pathways, depleting ergosterol and causing ignosterol to accumulate in the fungal cytoplasmic cell membranes. Amorolfine is marketed as Curanail, Loceryl, Locetar, and Odenil. It is available in the form of a 5% amorolfine nail lacquer used to treat onychomycosis (fungal infection of the toe- and fingernails). Amorolfine 5% nail lacquer in once or twice weekly applications is 60-71% effective in treating toenail onychomycosis; complete cure rates three months after stopping treatment (after six months of treatment) were 38-46%. However, full experimental details of these trials were not available and since they were first reported in 1992 there have been no subsequent trials.
It is a topical solution for the treatment of toenail infections. Systemic treatments may be considered more effective.
It is approved for sale over the counter in Australia and the UK (recently re-classified to over the counter status), and is approved for the treatment of toenail fungus by prescription in other countries. It is not approved for the treatment of onychomycosis in the United States or Canada.

Definition

ChEBI: A member of the class of morpholines that is cis-2,6-dimethylmorpholine in which the hydrogen attached to the nitrogen is replaced by a racemic 2-methyl-3-[p-(2-methylbutan-2-yl)phenyl]propyl group. An inhibitor of the action f squalene monooxygenase, Delta14 reductase and D7-D8 isomerase and an antifungal agent, it is used (generally as its hydrochloride salt) for the topical treatment of fungal nail and skin infections.

Indications

For the treatment of skin infections, a 0.25 % cream preparation is applied once daily until clinical cure is achieved and then for a further 3–5d. For the treatment of nail mycoses caused by dermatophytes, yeasts, and moulds, a lacquer preparation containing 5 % amorolfine is painted onto the affected nail once or twice a week until the nail has regenerated. Treatment of onychomycoses normally needs to be continued for up to 1 year. Amorolfine is also active in the treatment of vaginal candidiasis.

Antimicrobial activity

Amorolfine is a broad-spectrum antimycotic with in vitro activity against dermatophytes, pathogenicCandida species, and a variety of pathogenic dimophic fungi such as Blastomyces dermatitidis, Histoplasma capsulatum, and Sporothrix schenckii. The substance also shows some activity against various isolates of Aspergillus species.

Pharmacokinetics

Amorolfine is not absorbed after topical administration on normal skin. After application of a single vaginal tablet containing 50 mg of amorolfine, plasma concentrations between 27 and 83 ng/mL were observed.

Clinical Use

Amorolfine is the only drug in this class that is employed clinically in the treatment of human fungal infections. Amorolfine is not currently available in the United States, but it is marketed in Europe and Asia for the topical treatment of dermatophytic infections.

Metabolism

Not Available