Nail incorporation kinetics of terbinafine in onychomycosis patients

Abstract

Patients with toe-nail onychomycosis were treated with terbinafine (250 mg daily, n = 20) for either 6 or 12 weeks in a randomized double-blind study. Plasma and distal nail clippings were taken before initiation of therapy and 1, 6, 12, 18, 24, 36 and 48 weeks thereafter. Analytical data of terbinafine extracted from nail clippings or plasma were obtained by high-performance liquid chromatography (HPLC). Nail extracts and isolated HPLC terbinafine peaks were analysed using a combined gas chromatography-mass spectroscopy system (GC-MS) for unequivocal identification of the drug. Terbinafine could be detected in the distal nail in the majority of the patients within 1 week of starting therapy. Maximum terbinafine levels of 0.52 and 1.01 micrograms/g were measured after 18 weeks in the 6- and 12-week treatment groups, respectively. While plasma levels decreased rapidly after termination of therapy terbinafine was detected in the nails as long as 30 weeks (6 weeks treatment) and 36 weeks (12 weeks treatment) after termination of therapy at a range of 0.28-0.19 microgram/g. The drug concentrations measured at all time points are well above the minimum inhibitory concentration (MIC) for dermatophytes and other fungi. These data suggest that the drug reaches the nail plate rapidly and persists there for several months after cessation of active treatment.

Oral Treatments for Toenail Onychomycosis

“…Eighteen trials were excluded for the following reasons: duplicate reports, 42,43,46,[48][49][50]52,53 combined hand and feet data or combined with topical data, 41,47,51,54,55,57 no mycology assessment, 56 protocol deviation, 45 and data not clearly presented. 44,58 …”

Clinical and Histological Aspects of Toenail Onychomycosis Caused by <i>Aspergillus</i> spp.: 34 Cases Treated with Weekly Intermittent Terbinafine

“…Its persistence at effective concentrations in nails makes weekly administration of the drug a real option. Terbinafine has a high affinity for keratinized tissue: it reaches the nail bed within a week of starting therapy and persists in the nail plate for at least 30 weeks after the end of treatment [14, 15]. The effectiveness of pulsed terbinafine therapy in dermatophytic onychomycosis has recently been demonstrated [41, 42, 43, 44, 45].…”

“…are regarded as emerging fungal agents of toenail onychomycosis, and topical therapy does not seem to be effective; in contrast, systemic treatment with continuous terbinafine or pulsed itraconazole is very effective [10]. Because the risk-benefit consideration is important in systemic antifungal therapy, in the present study, we chose an intermittent regimen of oral terbinafine for 3 main reasons: (1) terbinafine is particularly effective against Aspergillus species [11, 12, 13]; (2) effective concentrations of terbinafine persist in the nail making weekly administration of the drug possible [14, 15]; (3) terbinafine is well tolerated, and side-effects and drug interactions are rare.…”

Grenzen der Kurzzeitbehandlung von Onychomykosen

“…und verweilt darüber hinaus noch eine längere Zeit im Nagelkeratin [6]. Itraconazol zeichnet sich durch seine sehr lange Verweildauer in ausreichend hohen Konzentrationen, die deutlich über den MHK der meisten Dermatophyten liegen, im Nagelkeratin aus [2].…”