Itraconazole penetrates the nail via the nail matrix and the nail bed-an investigation in onychomycosis

Matthieu, L.; Doncker, P. De; Cauwenbergh, G.; Woestenborghs, Robert; Velde, Vera Van de; Janssen, P. A. J.; Dockx, P.

doi:10.1111/j.1365-2230.1991.tb00405.x

Cited by 108 publications

(42 citation statements)

References 6 publications

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“…When the nail plate is tightly bound to the underlying nail bed, systemic antifungals normally reach the nail plate via rapid diffusion across the nail bed [33][34][35]. In a study of 18 patients who were treated with a course of oral terbinafine or itraconazole for onychomycosis, in the 5 nonresponders, there was involvement of the lateral edge of the nail plate.…”

Section: Nail Featuresmentioning

confidence: 99%

“…The final score is calculated by multiplying the scores for area of involvement and proximity of disease to the matrix, and then potentially adding points for dermatophytoma or severe hyperkeratosis. Final scores range from 0 to 35 and are broken down into mild (1-5), moderate (6)(7)(8)(9)(10)(11)(12)(13)(14)(15) and severe (16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35) categories, with a clinical cure receiving a score of zero [11]. Advantages of this system are that it is relatively simple to use, has been validated, and was shown to have high statistical reliability between dermatology experts in nail diseases and dermatologists who were generalists.…”

Section: Scoring Systems Used To Predict Prognosismentioning

confidence: 99%

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Prognostic Factors in Onychomycosis Treatment

Lipner

Scher

2014

J Infect Dis Ther

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Onychomycosis is a common fungal disease of the nail unit with a prevalence of 10% to 12% in the United States. Despite therapeutic innovations in the last few decades, as many as 20-25% of patients do not achieve a complete cure, and 10-53% are reported to relapse after successful treatment. Some of the factors associated with a poor response to onychomycosis have been well studied. They include patient characteristics and morbidities, nail characteristics, and the infecting organism. Therefore, the goal of therapy is to identify these specific prognostic features for each patient and devise an appropriate treatment plan that will allow for the best chance for cure. Scoring systems may be helpful for grading the severity of onychomycosis and predicting the therapeutic outcome.

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Section: Nail Featuresmentioning

confidence: 99%

Section: Scoring Systems Used To Predict Prognosismentioning

confidence: 99%

Prognostic Factors in Onychomycosis Treatment

Lipner

Scher

2014

J Infect Dis Ther

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“…The CV% of posaconazole exposure in toenails was higher than that in plasma (51% to 137% for the toenail C max versus 50% to 76% for the plasma C min ). Posaconazole diffusion into the nail plate, presumably via the nail plate bed, is likely to be consistent with that observed for other systemically administered antifungals, such as terbinafine, itraconazole, and fluconazole (1,2,5). Levels of posaconazole in the nail remained high after treatment was discontinued, probably because posaconazole accumulated in the nail matrix via systemic absorption during treatment.…”

mentioning

confidence: 67%

Determination of Posaconazole Levels in Toenails of Adults with Onychomycosis following Oral Treatment with Four Regimens of Posaconazole for 12 or 24 Weeks

Krishna

Martinho

et al. 2011

Antimicrob Agents Chemother

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Pharmacokinetic data from a randomized, parallel-group, multicenter study are presented. Adults with toenail onychomycosis (n ‫؍‬ 146) received posaconazole (100 mg, 200 mg, or 400 mg) once daily (QD) for 24 weeks or 400 mg QD for 12 weeks. The posaconazole concentration in the great toenail exhibited a dose-related increase starting at week 2 for 24 weeks and a mean toenail-to-plasma concentration ratio of approximately 3:1 at the end of treatment for the 400-mg 24-week dose.Posaconazole, a triazole antifungal, has potent in vitro activity against dermatophyte pathogens of onychomycosis (3). Pharmacokinetic (PK) data exist for the distribution of posaconazole within the skin (4), but no PK data exist for posaconazole distribution in toenails. This article presents PK data from a phase 2 clinical trial of posaconazole in the treatment of onychomycosis (ClinicalTrials.gov identifier NCT00491764).(Parts of this work were presented at the 68th Annual Meeting of the American Academy of Dermatology, Miami Beach, FL, 5 to 9 March 2010).This was a randomized, placebo-and active-controlled, parallel-group, multicenter, investigator-blinded study. After a 12-or 24-week treatment period, all patients were followed until 48 weeks after their first dose (i.e., a 24-or 36-week follow-up period). Patients received posaconazole at 100 mg, 200 mg, or 400 mg once daily (QD) for 24 weeks or 400 mg QD for 12 weeks, terbinafine (250 mg QD for 12 weeks), or a placebo (matched to posaconazole) for 24 weeks. Only patients receiving posaconazole were included in this PK analysis.The study protocol was approved by an appropriate ethics committee or institutional review board at each center and was carried out in accordance with good clinical practices. Written informed consent was obtained from each patient before enrollment. Patients were ages 18 to 75 years, had a clinical and mycologic diagnosis of onychomycosis affecting ϳ25% to 75% of at least 1 great toenail, and were otherwise in good health. Patients receiving systemic antifungal therapy within 3 months of study entry or topical foot or toenail antifungal therapy within 1 month of study entry were excluded, as were patients taking drugs known to interact with or be metabolized by cytochrome P450 3A4 within 2 weeks of randomization. Patients could not be pregnant or breastfeeding.Predose blood and toenail samples were collected from all 10 toes at each visit (day 1 and weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and 48). Toenail clippings (without subungual debris) were obtained and stored frozen at Ϫ20°C until they were shipped to Covance Laboratories Inc., Madison, WI, for assay. A validated standard curve was constructed with untreated human nails from healthy volunteers as the matrix. Toenail samples were mixed with 1.00 ml of 1 M sodium hydroxide per 10.0 mg of toenail, placed in a shaking water bath at 70°C for at least 1 h, and then vortexed for ϳ30 s. Hydrolyzed toenail solution (1.00 ml) was mixed with methanol-water (50:50 [vol/vol]; 0.05 ml) and ethyl acetate-...

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“…Pilot study 11 Toenail of fingernail [ [10][11][12][13][14][15][16]. The diffusion of the drug into the distal part of the nail occurs via nail bed that is further confirmed due to the presence of two foldhigher drug concentration in subungual nail material than in distal nail clippings of a patient treated for one month.…”

Section: Second Generation Oral Antifungalsmentioning

confidence: 99%

“…The drug reaches the nail plate within 24 h of administration and can be observed in the distal part of the nail plate even after one month of initiation of therapy Effective in the long-term therapy of onychomycosis. [10] Open-labelled, non-comparative study 16 Finger and toenail 150 mg daily for 6 months * No adverse effect was observed.…”

Section: Second Generation Oral Antifungalsmentioning

confidence: 99%