Levels of terbinafine in plasma, stratum corneum, dermis-epidermis (without stratum corneum), sebum, hair and nails during and after 250 mg terbinafine orally once daily for 7 and 14 days.
In earlier skin pharmacokinetic studies we have shown that terbinafine is rapidly delivered to the stratum corneum, nails and hair both through sebum and by direct diffusion through dermis-epidermis. In the present study the skin pharmacokinetic profile of terbinafine was studied in two groups of eight human male volunteers during and after 250 mg orally once daily for 7 and 14 days. In the 7-day study high terbinafine levels were found in sebum (19.0 micrograms/g) and stratum corneum (2.5 micrograms/g), and a concentration in stratum corneum above the minimal inhibitory concentration for most dermatophytes was still found 48 days after the last day of medication. Terbinafine was found in peripheral nail clippings after 7 days of medication and the concentration was, in the 7-day study, 0.5 microgram/g 1 day after stopping medication; it was still 0.2 microgram/g 90 days after stopping treatment. The results in the 14-day study were in parallel with, but higher than, in the 7-day study. The elimination of terbinafine from several compartments is biphasic, with a faster initial elimination followed by a slower secondary elimination. For nails, the elimination is slower compared with the other compartments. The results indicate that terbinafine may be effective in short-term treatment of several dermatophytoses. The concentration of 0.2 microgram/g of terbinafine found in nails 90 days after stopping medication, following 7 days of treatment, indicates that the duration of therapy, even in tinea ungium, may be shorter than is currently the case.
Faergemann
J
J
Department of Dermatology, University of Gothenburg, Sahlgren's Hospital, Sweden.
Zehender
H
H
Millerioux
L
L
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000935:Antifungal Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004334:Drug Administration Schedule; D006801:Humans; D008297:Male; D008875:Middle Aged; D009281:Naphthalenes / Q000008:administration & dosage / Q000493:pharmacokinetics*; D012629:Sebum / Q000378:metabolism; D012867:Skin / Q000378:metabolism*; D000077291:Terbinafine; D014344:Trypanocidal Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*
D000935:Antifungal Agents; D009281:Naphthalenes; D014344:Trypanocidal Agents; D000077291:Terbinafine