Itraconazole pulse therapy for onychomycosis and dermatomycoses: An overview

Doncker, P. De; Gupta, Aditya K.; Marynissen, G.; Stoffels, Paul; Heremans, Annie

doi:10.1016/s0190-9622(97)70074-4

Cited by 81 publications

(82 citation statements)

References 40 publications

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“…As was seen in the first two studies, all treatment groups were significantly superior to the untreated control groups in regard to the clinical and mycological endpoints (P Ͻ 0.001; Table 3). The efficacy profile observed with itraconazole and terbinafine when dosed once weekly is consistent with their reported clinical efficacies when dosed in a noncontinuous manner (25,26). For a visual indication of the severity of infection and the degree of antifungal effect, Fig.…”

Section: Vt-1161 Mics Against Dermatophytessupporting

confidence: 80%

VT-1161 Dosed Once Daily or Once Weekly Exhibits Potent Efficacy in Treatment of Dermatophytosis in a Guinea Pig Model

Garvey

Hoekstra

Moore

et al. 2015

Antimicrob Agents Chemother

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c Current therapies used to treat dermatophytoses such as onychomycosis are effective but display room for improvement in efficacy, safety, and convenience of dosing. We report here that the investigational agent VT-1161 displays potent in vitro antifungal activity against dermatophytes, with MIC values in the range of <0.016 to 0.5 g/ml. In pharmacokinetic studies supporting testing in a guinea pig model of dermatophytosis, VT-1161 plasma concentrations following single oral doses were dose proportional and persisted at or above the MIC values for at least 48 h, indicating potential in vivo efficacy with once-daily and possibly once-weekly dosing. Subsequently, in a guinea pig dermatophytosis model utilizing Trichophyton mentagrophytes and at oral doses of 5, 10, or 25 mg/kg of body weight once daily or 70 mg/kg once weekly, VT-1161 was statistically superior to untreated controls in fungal burden reduction (P < 0.001) and improvement in clinical scores (P < 0.001). The efficacy profile of VT-1161 was equivalent to those for doses and regimens of itraconazole and terbinafine except that VT-1161 was superior to itraconazole when each drug was dosed once weekly (P < 0.05). VT-1161 was distributed into skin and hair, with plasma and tissue concentrations in all treatment and regimen groups ranging from 0.8 to 40 g/ml (or g/g), at or above the MIC against the isolate used in the model (0.5 g/ml). These data strongly support the clinical development of VT-1161 for the oral treatment of onychomycosis using either once-daily or once-weekly dosing regimens. F ungal infections of the skin, nails, and hair by dermatophytes, yeasts, and nondermatophyte molds are a common occurrence (1-3), with an estimated worldwide prevalence of 20% to 25% (1). In a survey of ambulatory records in the United States, these infections necessitated an average of 4 million physician visits per year from 1995 to 2004 (4), and the majority of these infections were caused by dermatophytes. The worldwide distribution of causative fungi and types of infection are dependent on geography, environment, and cultural factors (1, 2). Consistent with most of Europe and the United States (1, 2), a recent retrospective study found that onychomycosis (also referred to as tinea unguium) was the most common dermatophyte infection and that the absolute number of onychomycosis cases increased 10-fold over a 40-year period (5). This increase can be partly explained by the increases of two at-risk populations, the elderly (6) and diabetics (7). The most common species causing onychomycosis in Europe and the United States are Trichophyton rubrum, Trichophyton mentagrophytes, and Epidermophyton floccosum (8).Current oral treatment options for superficial fungal infections include allylamines, such as terbinafine, and azole-based fungal sterol 14␣-demethylase (CYP51) inhibitors (8, 9). The azoles fall into two classes defined by the moiety that binds the heme iron within the active site of CYP51, the imidazoles (e.g., ketoconazole), which are rarely used orally due...

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Section: Vt-1161 Mics Against Dermatophytessupporting

confidence: 80%

VT-1161 Dosed Once Daily or Once Weekly Exhibits Potent Efficacy in Treatment of Dermatophytosis in a Guinea Pig Model

Garvey

Hoekstra

Moore

et al. 2015

Antimicrob Agents Chemother

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“…Inclusion criteria for subjects included those aged 12 to 70 years who had a clinical diagnosis of pityriasis versicolor confirmed by mycological examination and who provided written informed consent before inclusion into the trial. Exclusion criteria for subjects included those with (1) known sensitivity to itraconazole or its excipients, (2) chronic mucocutaneous candidiasis or systemic fungal infection, (3) immunosuppression caused by disease or treatment, (4) any other disease or condition that in the investigator's opinion should exclude the patient from the trial, and those who (5) participated in an investigational drug trial within 30 days of selection, (6) were pregnant or breastfeeding, and (7) were women of childbearing potential without adequate contraception. The following therapies were not allowed: (1) topical antifungal agents, topical corticosteroids, shampoos with active ingredients against Malassezia, or tar shampoos used within 2 weeks of the randomization visit or during the trial (topical corticosteroid nasal sprays or eye ointments were allowed during the trial); (2) systemic corticosteroid therapy either within 1 month of the randomization visit or during the trial; (3) systemic antifungal therapy within 2 months of the randomization visit or during the trial; (4) use of the enzymeinducing drugs rifampin, phenytoin, rifabutin, carbamazepine, and isoniazid; and (5) use of some drugs metabolized by cytochrome P4503A4 with concomitant increase in their concentrations (eg, terfenadine, astemizole, cisapride, oral midazolam hydrochloride, triazolam, quinidine gluconate, pimozide, and 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors).…”

Section: Methodsmentioning

confidence: 99%

“…4,5 When itraconazole is used to treat pityriasis versicolor, a suggested regimen is 200 mg/d for 7 days, with a minimum cumulative dose of at least 1000 mg being required for effective therapy. 6,7 Four weeks after the start of therapy, cure rates of 80% to 90% have been reported. 7 Although the fungal organisms may be nonviable, the color of the affected skin may take several weeks or months to normalize.…”

Section: 2mentioning

confidence: 99%

Efficacy of Itraconazole in the Prophylactic Treatment of Pityriasis (Tinea) Versicolor

Faergemann

Gupta²,

Mofadi³

et al. 2002

Arch Dermatol

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“…Pulse therapy with itraconazole embodies dosing for 1 week (pulse) per month for a set number of months [17]. The instances of regimens that have been investigated for safety and efficacy in randomized trials included a three and a four pulse regimen with doses of 200 mg of itraconazole twice daily [18,19] and a two pulse regimen with 200 mg of itraconazole twice daily [17,[20][21][22]. Data from clinical practice and clinical trials indicate that the 1-week pulse regimen of itraconazole is well tolerated and associated with a favorable safety profile [23].…”

Section: Second Generation Oral Antifungalsmentioning

confidence: 99%