Update on terbinafine with a focus on dermatophytoses

Figures & data

Table 1 Pharmacokinetic parameter estimates of terbinafine following oral administration

Parametera	Adults 125 mg single-dose (n = 26)^Citation43,Citation44	Adults 250 mg single-dose (n = 29)^Citation45,Citation46	Adults 125 mg steady-state (n = 10)^Citation43	Adults 250 mg steady-state (n = 22)^Citation46,Citation47	Children 125 mg single-dose (n = 28)^Citation43,Citation44	Children 125 mg steady-state (n = 16)^Citation43
Tmax (h)	1.3–1.5	1.4–1.5	1.6	1.2	1.7–2.1	1.8
Cmax (ng/mL)	506–565	1340–1656	646	1700b	706–909	1059
AUC (h*ng/mL)	1624–2135	4740–6762	3720	10481	2967–4104	5851
Cl/F (L/h/kg)	1.2	0.55	0.4		1.9	1.7
Vss/F (L/kg)	19.2		19.5
t1/2α (h)	0.7	0.35		1.2
t1/2β (h)	26.7	12.6–14.2	14.7
t1/2γ (h)				396	156

a Notes: Values represent the mean reported values from the referenced studies (when more than one study is referenced, values represent the range of reported mean values).

b Corresponding peak tissue concentrations: hair, 2.4 μg/g; stratum corneum, 14.4 μg/g; sebum, 56.1 μg/g.

Abbreviations: T_max, time at maximum plasma concentration; C_max, maximum plasma concentration; AUC, area under the plasma concentration vs time curve; Cl/F, apparent oral clearance; Vss/F, steady-state volume of distribution; t_1/2α, alpha-phase half-life; t_1/2β, beta-phase half-life, t_1/2γ, gamma-phase or terminal half-life.

Table 2 Local and systemic estimates of exposure following topical terbinafine application

Parametera	1% gel × 7 days healthy skin^Citation48,Citation49	1% cream 7 days^Citation48,Citation50,Citation54	1% FFS 1 application^Citation50
Stratum corneum Cmax (μg/cm^2)	0.91	0.94–2	5
Stratum corneum AUC (h*μg/cm^2)	12.7	11.7–13.5	104.2
Tissue t1/2 (h)	1.2	68	162
Plasma Cmax (ng/mL)	3.82
Plasma AUC (h*ng/mL)	63

a Notes: Values represent the mean reported values from the referenced studies (when more than one study is referenced, values represent the range of reported mean values).

Abbreviations: C_max, maximum observed concentration, AUC, area under the concentration vs time curve; t_1/2, half-life.

Table 3 Case-reports and open-label studies examining terbinafine use in non-dermatophyte infections

Organism	Site	Dosing regimen	Outcome	Reference
Aspergillus spp.	toenail	500 mg/day (pulse: 1 wk/mos) 3 months	clinical and mycological cure (88%)	^Citation168
Aspergillus flavus	musclea	250 mg daily 13 weeks	resolution	^Citation169
Aspergillus sydowii	toenail	500 mg/day (pulse: 1 wk/mos)b 3 months	failure	^Citation128
Aspergillus ustus	skina	not providedc 11 months	resolution	^Citation170
Cladosporium carrionii	skin	500 mg daily 4–12 months	cure or clinical improvement (83%–100%)	^Citation171, ^Citation172
Curvularia lunata	heart valve (endocarditis)	125 mg twice dailyd,e 7 years	tissue mycologically negative	^Citation173
Fonsecaea monophora	skin	250 mg dailyb 7–10 weeks	clinical and mycological cure	^Citation174
Fonsecaea pedrosoi	skin	500 mg daily 4–12 months	cure or clinical improvement (83%–100%)	^Citation171,Citation172
Paecilomyces lilacinus	cornea (keratitis)	250 mg once dailyb,c 10–12 weeks	resolution	^Citation175, ^Citation176
Paracoccidoides brasiliensis	perineum/scrotum	250 mg twice daily 6 months	resolution	^Citation177
Piedra hortae	scalp	250 mg once daily 6 weeks	effective	^Citation178
Phialphora parasitica	disseminateda	125 mg twice daily 2 months	drug discontinued	^Citation179
Sporothix schenckii	cutaneous/subcutaneous	250 mg twice daily range: 8–37 weeks	success	^Citation180, ^Citation181

a Notes: Patient immunocompromised or immunosuppressed;

b Concurrent treatment with itraconazole;

c Concurrent treatment with voriconazole;

d Concurrent treatment with amphotericin B;

e Concurrent treatment with ketoconazole.

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