Systemic treatments

Currently, systemic treatment is the most effective method of curing onychomycosis. Even so, between 20-25% of patients fail to respond [11]. Terbina-fine (1) and itraconazole (2) are the two systemic treatments of choice with ter-binafine showing greater efficacy than itraconazole and lower rates of recurrence

Terbinafine (1), a representative of the allylamine class of antifungal agents, inhibits squalene epoxidase [16,17] and thereby prevents the biosynthesis of ergos-terol, a key ingredient in the fungal cell wall. Terbinafine is active against dermatophytes, M. furfur, Aspergillus species and some Candida species including C. parapsilosis; however, it is fungistatic against C. albicans [2]. A single oral dose of 250 mg terbinafine given to humans produces peak plasma concentrations of 1 mg| mL within two hours [14]. It is > 99% protein bound and has a half-life of about 36 hours. It is administered at a dose of 250mg once daily for 6 weeks for finger nails or 12 weeks for toe nails [14]. One study showed that terbinafine localizes in the stratum corneum via sebum [18]. Terbinafine has a cLogP of 6.5 and a molecular weigh of 292 Da.

Itraconazole (2), which is from the azole class of antifungal agents, inhibits la-nosterol 14 a-demethylase and thus stops the biosynthesis of ergosterol. It has broad spectrum activity against species including dermatophytes, Candida species, Aspergillus species and M. furfur [2]. Blood levels of itraconazole after a single 200mg dose given to humans reached a peak level of 0.2-0.3 mg/mL after 4-5 hours [15]. It is 99.8% protein bound and has a half-life of 21 hours. It is administered either 200 mg once daily for 12 weeks or 200 mg twice daily for 7 days followed by 3 weeks with no treatment and repeated for three months. Like terbinafine,

itraconazole also localizes in the stratum corneum via sebum but at much lower levels [18,19]. Itraconazole has a cLogP of 3.3 and molecular weight of 706 Da.

Griseofulvin (3), isolated from Pénicillium griseofulvin in 1939 [20], has a limited spectrum of activity. It is fungistatic against dermatophytes only and works by binding to microtubular proteins thus inhibiting cell mitosis. It has a cLogP of 2.2 and a molecular weight of 353 Da.

The commonly used antifungal agent, fluconazole, has also been prescribed, offlabel, for the treatment of onychomycosis.

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