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

Abstract

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.

Multiple-dose pharmacokinetics and distribution in tissue of terbinafine and metabolites

“…Because of the limited duration of blood sampling and the assay limit of quantification, a third disposition phase was not observed in these early single-dose studies. Only in subsequent multiple-dose investigations in which plasma washout kinetics were followed was a third disposition phase with a half-life of about 20 to 28 days clearly identifiable (4,13). The average t 1/2 of 17 days in the present investigation is in line with these results.…”

“…The concentrations in sebum and hair samples were severalfold higher than simultaneous concentrations in plasma samples. This is in agreement with a previous investigation employing a similar dosing schedule (4). In the present study terbinafine levels in stratum corneum samples (about 1 g/ml) were lower than those previously reported (about 10 g/ml), which may have been due in part to intersubject variability and to the different sampling sites investigated (i.e., sole versus back [4]).…”

“…This is in agreement with a previous investigation employing a similar dosing schedule (4). In the present study terbinafine levels in stratum corneum samples (about 1 g/ml) were lower than those previously reported (about 10 g/ml), which may have been due in part to intersubject variability and to the different sampling sites investigated (i.e., sole versus back [4]). The levels in nail clippings were generally quantifiable by week 3 of multiple dosing, which is in agreement with the results of Finlay (5), who speculates that the early presence of terbinafine in distal nails indicates that it enters the nail plate across the whole nail bed and not primarily via the proximal growing nail matrix, the presumed entry route for other antifungal agents.…”

Development of terbinafine solid lipid nanoparticles as a topical delivery system

“…7,8 Moreover, the TB treatment duration is shorter in most cases. 9,10 Based on several clinical studies conducted in humans [11][12][13] and animals, 14,15 it was noted that TB accumulates in the skin and persists at high concentrations for up to several weeks after discontinuing drug application. The superior efficacy of TB after the end of the treatment period is attributed to its fungicidal effect in addition to the favorable pharmacokinetic characteristics of substantial and rapid penetration into the stratum corneum (SC), where it remains in the skin for a long time after discontinuing treatment.…”

Antifungal agents for common outpatient paediatric infections

“…It diffuses to keratinocytes from the blood stream to reach the stratum corneum and hair follicles (42). Because it is not metabolized through cytochrome P-450, many of the drug interactions seen with the azoles do not occur.…”