Terbinafin

Future Antimycotics for Systemic Treatment. Two new antimycotics for systemic use have now reached the stage of clinical development. The first is a triazole and fluoride analogue of itraconazole. This compound (saperconazole) is extremely active 2i 2cm.%. Jisperpillus spp. and slightly more soluble. Consequentiy, intravenous adruinistration might be possible (34). The second molecule is terbinafine [91161 -71 -6] an aHylamine, C21H25N, that appears to be particularly active against dermatophytes, just like topical naftifine (35). 

H. Zehender, J. Denouel, M. Roy, E. Ee Saux and P. Schaub, Simultaneous determination of terbinafine (Eamisil) and five metabolites in human plasma and urine by liigh-peifoimance liquid cliromatogi aphy using on-line solid-phase exti action , 7. Chromatogr. B 664 347-355 (1995). 

Due to the divergence of fungal diseases, there is neither single best treatment nor a superior drug for all diseases. However, a superior drug does exist for dermatomycoses caused by dermatophytes, namely the allylamine terbinafine (TER). For the treatment of deep mycoses in immunosuppressed patients the most efficacious drug is the polyene Amph B. 

This is not discussed in detail since mechanisms of resistance have been carefully reviewed (Ghannoum and Rice 1999). It was pointed out that resistance has not been associated with modification of the structure. For the 1,2,4-triazoles that have been widely used, their effect is due to inhibition of the synthesis of ergosterol that is the dominant component of fungal cell membranes. Resistance is generally associated with modification of the target enzymes, for example, the epoxidation of squalene (Terbinafine) or 14a-demethylase (Fluconazole). Resistance of Candida albicans to the azole antifungal agent fluconazole demonstrated, however, the simultaneous occurrence of several types of mechanism for resistance (Perea et al. 2001) ... 

Onychomycosis is a chronic infection that rarely remits spontaneously. Adequate treatment is essential to prevent spread to other sites, secondary bacterial infections, cellulitis, or gangrene. Due to the chronic nature and impenetrability of nails, topical agents have low efficacy rates for treating onychomycosis. Oral agents that can penetrate the nail matrix and nail base, such as itraconazole and terbinafine, are more effective than ciclopirox lacquer. Itraconazole and terbinafine demonstrate mycological cure rates of 62%37 and 76%,38 respectively, while ciclopirox has a cure rate of 29% to 36%.39... 

Topical agents with minimal pregnancy risk include bacitracin, benzoyl peroxide, ciclopirox, clindamycin, erythromycin, metronidazole, mupi-rocin, permethrin, and terbinafine. 

A more recent addition to the list of drugs that have been associated with a lupus-like syndrome is terbinafine [23,24], This drug is also metabolized to a reactive metabolite [25], and it has a very long half-life in the skin, which likely explains why the dominant manifestations of lupus associated with this drug are in the skin. 

Bonsmann, G. et al, Terbinafine-induced subacute cutaneous lupus erythematosus, J. Amer. Acad. Dermatol., 44, 925, 2001. 

Iverson, S.L. and Uetrecht, J.P., Identification of a reactive metabolite of terbinafine Insights into terbinafine-induced hepatotoxicity, Chem. Res. Toxicol., 14, 175, 2001. 

Brignol N. et al., 2000. Quantitatived analysis of terbinafine (Lamisil ) in human and minipig plasma by liquid chromatography tandem mass spectrometry. Rapid Commun Mass Spectrom 14 141. 

Use of a hERG blocker in a patient also taking CYP3A4 inhibitors (e.g. antibacterial macrolides, azole antifungals, HIV protease inhibitors) or CYP2D6 inhibitors (quinidine, halofantrine, fluoxetine, paroxetine, thioridazine, terbinafine) the hERG blocker, if mostly metabolized by these CYP isoforms, may accumulate because... 

Terbinafine is available for oral administration and is indicated for fungal nail infections. Treatment with terbinafine for nail infections can take up to 3 months depending on the condition, with a minimum duration of 6 weeks. Photosensitivity may occur as a side-effect to terbinafine. 

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