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Biomedical subjects

R K Scher

Publications and source records attributed to R K Scher.

At least 37 records · Page 2Linked to original sources
PubMed1998

Once-weekly fluconazole (150, 300, or 450 mg) in the treatment of distal subungual onychomycosis of the fingernail.

BACKGROUND: Onychomycosis is a prevalent infection of the nail caused primarily by dermatophytes. Fluconazole is active in vitro against the most common pathogens, penetrates into the nail bed, and is clinically effective in the treatment of a wide variety of fungal infections. OBJECTIVE: The purpose of this study was to assess the safety and efficacy of oral fluconazole 150, 300, and 450 mg administered once weekly compared with placebo in the treatment of distal subungual onychomycosis of the fingernail caused by dermatophytes. METHODS: This was a multicenter, randomized, double-blind, placebo-controlled study enrolling 349 patients with onychomycosis of the fingernails. Clinical and mycologic efficacy as well as measures of safety were assessed monthly for a maximum of 9 months of treatment, with additional safety visits occurring at weeks 2 and 6. For inclusion, patients were required to have clinically and mycologically documented onychomycosis of the fingernail caused by dermatophytes with at least 25% involvement of the target fingernail. After end of therapy, patients with improved or cured fingernails entered a blinded 6-month follow-up without drug treatment during which efficacy was assessed every 2 months. Efficacy was assessed by clinical (visual) and mycologic (microscopic and culture) measures. Clinical measures included assessments of the percentage of target nail involvement, measurement of the distance from the nail fold to the proximal onychomycotic border, and signs and symptoms of onychomycosis. RESULTS: Fluconazole was significantly superior to placebo in eradicating clinical and mycologic symptoms of onychomycosis, both at the end of active treatment and at 6 months after treatment (p=0.0001 for all efficacy measures). At the end of therapy, 91% to 100% of patients in the fluconazole groups were judged clinical successes, defined as reduction of the affected area of the target nail to less than 25% or cure, compared with 8% for placebo. Clinical cure rates at end of therapy were 76%, 85%, and 90% for fluconazole 150, 300, and 450 mg, respectively, compared with 3% for placebo. These clinical success and cure rates were largely maintained or improved during follow-up. Clinical relapse in cured patients during the follow-up period was very low (1.5% to 3.3%). Fluconazole demonstrated mycologic eradication rates of 89% to 100% at the end of treatment and 90% to 99% at the end of follow-up; for placebo the rates were 8% and 12%, respectively. CONCLUSION: Fluconazole administered once weekly is safe and effective in eradicating distal subungual onychomycosis of the fingernail caused by dermatophytes.

Adolescent↗
PubMed1998

Pharmacokinetics of three doses of once-weekly fluconazole (150, 300, and 450 mg) in distal subungual onychomycosis of the toenail.

BACKGROUND: Preliminary clinical data suggest that fluconazole is effective in the treatment of patients with onychomycosis. To design optimum dosage regimens, a better understanding of fluconazole's distribution into and elimination from nails is needed. OBJECTIVE: The purpose of this study was to determine plasma and toenail concentrations of fluconazole. METHODS: In this multicenter, randomized, double-blind investigation, fluconazole (150 mg, 300 mg, or 450 mg) or matching placebo was administered once a week for a maximum of 12 months to patients with onychomycosis of the toenail. A total of 151 subjects participated in the pharmacokinetic assessment. Blood samples and distal toenail clippings from both affected and healthy nails were obtained for fluconazole concentration determinations at baseline, at the 2-week visit, at each monthly visit until the end of treatment, and then at 2, 4, and 6 months (nail samples only at the latter two) after fluconazole was discontinued. RESULTS: Fluconazole was detected in healthy and affected nails at the 2-week assessment in nearly all subjects. The median time to reach steady-state fluconazole concentrations in healthy nails was 4 to 5 months in the three fluconazole dose groups. In affected nails, steady-state fluconazole concentrations were achieved more slowly, with a median time of 6 to 7 months. At the 8-month assessment, affected toenail fluconazole concentrations were higher than corresponding plasma fluconazole concentrations, with ratios of 1.31 to 1.50 in the three active treatment groups. Toenail concentrations of fluconazole declined slowly after treatment was discontinued, with elimination half-lives of 2.5, 2.4, and 3.7 months for the 150, 300, and 450 mg doses, respectively. Measurable fluconazole concentrations were still present in toenails at 6 months after treatment in most subjects. CONCLUSION: Fluconazole penetrates healthy and diseased nails rapidly, yielding detectable concentrations after two weekly doses. Once it penetrates nail, fluconazole persists for up to 6 months or longer after therapy is stopped. These favorable pharmacokinetic characteristics support a once-weekly fluconazole dosage regimen for the treatment of patients with onychomycosis.

Antifungal Agents↗
PubMed1998

Pharmacokinetics of three once-weekly dosages of fluconazole (150, 300, or 450 mg) in distal subungual onychomycosis of the fingernail.

BACKGROUND: Fluconazole has proven to be safe and effective for a variety of superficial and systemic fungal infections. Preliminary analysis of extensive Phase III studies suggests that it is very effective for the treatment of onychomycosis. Its pharmacokinetic properties, including low molecular weight and high water-solubility, suggest a unique ability to penetrate the nail. This feature is likely to account in part for fluconazole's effectiveness in the treatment of onychomycosis. OBJECTIVE: Determinations of plasma and fingernail concentrations of fluconazole were performed as part of a larger study comparing the safety and efficacy of once-weekly fluconazole (150, 300, and 450 mg) to placebo in the treatment of distal subungual onychomycosis of the fingernails caused by dermatophytes. The relationship between fluconazole concentrations and efficacy was also examined. METHODS: Pharmacokinetic studies were performed by means of plasma and fingernail samples from 133 patients, a subset of 349 patients participating in a double-blind, placebo-controlled clinical trial of fluconazole administered in once-weekly doses of 150, 300, or 450 mg until cure of onychomycosis or for a maximum of 9 months. Blood and fingernail samples for pharmacokinetic analysis were taken at baseline, at week 2, and at monthly intervals during the treatment phase of the study. Patients considered clinically cured or improved also participated in a 6-month follow-up study. During this phase, patients were monitored and samples taken every 2 months. RESULTS: Significant amounts of fluconazole were detected in the earliest fingernail samples taken (after 2 weeks of treatment). After two weekly doses, 30% to 33% of steady-state concentrations had been achieved in healthy nails and 22% to 29% in affected nails. Steady state was achieved in 3 to 5 months. Fluconazole concentration in nails as well as plasma followed dose-proportional pharmacokinetics. Nail:plasma ratios in affected nails were 0.4 to 0.6 at 2 weeks and 1.7 to 1.8 at 6 months. Fluconazole concentrations fell slowly after drug discontinuation and were still detectable 4 months after end of treatment. A statistically significant correlation was found between steady-state concentration and clinical and global outcomes. CONCLUSION: Fluconazole rapidly penetrates the fingernail, where it is retained at detectable levels for at least 4 months after drug discontinuation. A significant correlation exists between fluconazole concentration in the fingernails and clinical and global outcomes.

Adult↗
PubMed1998

Itraconazole for the treatment of onychomycosis.

BACKGROUND: The broad spectrum of activity of itraconazole in vitro manifests itself clinically with the drug being effective for the treatment of onychomycosis caused by dermatophytes, Candida and some non-dermatophyte molds. The pharmacokinetics of itraconazole in the nail results in drug remaining at therapeutic levels for 6-9 months after completion of therapy. METHODS: An overview of studies where continuous or pulse itraconazole therapy has been used in the treatment of fingernail and toenail onychomycosis. RESULTS: Following continuous therapy at 200 mg/day for 3 months for toenail onychomycosis (n = 1741), the rates of clinical cure, clinical response and mycologic cure were: (meta-average +/- 95% standard error (SE)), 52 +/- 9%, 86 +/- 2%, and 74 +/- 3%, respectively, at follow-up 12 months following start of therapy. In fingernail onychomycosis (n = 211), the duration of therapy was 6 weeks and the corresponding efficacy rates at follow-up, 9 months after start of therapy, were meta-average (+/- S.E.) 82 +/- 5%, 90 +/- 2%, and 86 +/- 3%, respectively. In toenail onychomycosis treated with 3 pulses of therapy (n = 1389), the clinical response, clinical cure and mycologic cure were observed in meta-average (+/- S.E.) 58 +/- 10%, 82 +/- 3%, and 77 +/- 5% patients, respectively, at follow-up 12 months after the start of therapy. In fingernail onychomycosis treated with 2 pulses of therapy (n = 210), at follow-up 9 months after the start of therapy, the corresponding efficacy rates were meta-average (+/- S.E.) 78 +/- 10%, 89 +/- 6%, and 87 +/- 8%, respectively. CONCLUSIONS: Both the continuous and pulse therapy regimens are safe with few adverse effects. Compared to continuous therapy, the pulse regimen has an improved adverse-effects profile, is more cost-effective, and is preferred by many patients.

Antifungal Agents↗
PubMed1998

Long-term remission of two feet-one hand syndrome.

Two feet-one hand syndrome is also defined as bilateral plantar tinea pedis with coexistent unilateral tinea manuum. Toenails and fingernails may also be affected and the dermatophyte Trichophyton rubrum is the usual cause. When there is nail involvement, especially of the toenails, treatment with an oral antifungal agent should be considered because topical therapy alone is usually not effective. However, relapses are common. With the advent of new, more effective antifungal drugs such as itraconazole, terbinafine, and fluconazole, it is hoped that this troublesome and recalcitrant disorder may be better controlled.

Adult↗
PubMed1997

Oral terbinafine in the treatment of toenail onychomycosis: North American multicenter trial.

BACKGROUND: Onychomycosis is an increasing problem with limited therapeutic options. OBJECTIVE: We evaluated the safety and efficacy, of oral terbinafine, a new fungicidal antimycotic, in patients with toenail onychomycosis. METHODS: A North American multicenter, double-blind, placebo-controlled study evaluated the mycologic and clinical efficacy of oral terbinafine 250 mg/day for 12 or 24 weeks in 358 patients with toenail onychomycosis. RESULTS: A total of 74% of patients treated with 12 or 24 weeks of terbinafine achieved a successful clinical outcome. Approximately 11% of terbinafine responders showed evidence of relapse 18 of 21 months after cessation of treatment. Terbinafine was well tolerated; most adverse events were transient and mild to moderate in severity. CONCLUSION: The results of this study confirm that oral terbinafine is a safe and effective therapy for the treatment of onychomycosis.

Abdominal Pain↗
PubMed1997

Itraconazole therapy is effective for pedal onychomycosis caused by some nondermatophyte molds and in mixed infection with dermatophytes and molds: a multicenter study with 36 patients.

BACKGROUND: Onychomycosis of the toenail caused by nondermatophyte molds alone or in combination with dermatophytes is difficult to eradicate with standard antifungal therapy. OBJECTIVE: Our purpose was to determine the effectiveness of itraconazole in the treatment of toenail onychomycosis caused by molds alone or in combination with dermatophytes. METHODS: We treated 36 patients with this drug given as continuous dosing (100 or 200 mg/ day) for 6 to 20 weeks or as a 1-week pulse dosing (200 mg twice daily for 1 week per month) for two to four pulses. RESULTS: Patients with toenail onychomycosis with the following organisms were treated: Aspergillus spp. (eight patients), Fusarium spp. (four patients), Scopulariopsis brevicaulis (23 patients), and Alternaria spp. (one patient). Nineteen patients had onychomycosis with a mixed origin. At follow-up, 12 months after therapy was initiated, clinical and mycologic cure was achieved in 15 of 17 patients (88%) with onychomycosis caused by a single mold. In patients with mixed infection, a clinical cure was obtained in 16 of 19 patients (84%) and a mycologic cure in 13 of 19 patients (68%). CONCLUSION: Itraconazole appears to be effective and safe for the treatment of toenail onychomycosis caused by some nondermatophyte molds alone or in combination with dermatophytes.

Antifungal Agents↗
PubMed1997

A multicenter, placebo-controlled, double-blind study of intermittent therapy with itraconazole for the treatment of onychomycosis of the fingernail.

BACKGROUND: Onychomycosis is the most frequent cause of nail disease and represents 30% of all mycotic infections of the skin. OBJECTIVE: Our purpose was to compare the effectiveness and tolerability of intermittent dosing of itraconazole ("pulse therapy") with placebo in fingernail onychomycosis. METHODS: Seventy-three patients with clinically and mycologically diagnosed fingernail onychomycosis were randomly selected to receive itraconazole, 200 mg twice daily, or placebo for the first week of each month for 2 consecutive months; patients were observed for 19 weeks. Seventy-one patients received the study medication and were included in the safety analysis. Efficacy of treatment was evaluated in 46 patients. RESULTS: A significantly greater proportion of itraconazole-treated patients than placebo-treated patients achieved clinical success (77% vs 0%), mycologic success (73% vs 13%), and overall success (68% vs 0%). No itraconazole-treated patient had a clinical or mycologic relapse during the follow-up period. Ten itraconazole-treated patients (28%) and nine placebo-treated patients (26%) had adverse events. Three patients discontinued treatment for safety reasons. CONCLUSION: Pulse therapy with itraconazole for 2 consecutive months produces significantly greater clinical, mycologic, and overall success than placebo. Short-term itraconazole pulse therapy for fingernail onychomycosis is effective and well tolerated.

Adult↗
PubMed1997

Current management of onychomycosis. An overview.

Until recently pedal onychomycosis, particularly when it affected several nails or involved a large nail plate area, was often regarded as untreatable. The advent of new therapies such as itraconazole, terbinafine, and fluconazole has been a significant and welcome addition to the armamentarium of therapies at the disposal of the physician. These drugs appear in the nail plate within days of starting oral therapy, being taken up by both the nail matrix and the nail bed. The duration required for effective therapy has been reduced, while the efficacy rates and cost-effectiveness have increased compared with the older treatments, such as griseofulvin. Some of the newer agents appear to have a wider spectrum of activity. Thus far, the newer agent have exhibited a low risk to benefit ratio. I may be possible to combine oral therapies with topical and surgical treatments, thereby further increasing efficacy rates and the cost-effectiveness while decreasing adverse effects and duration of oral therapy.

Antifungal Agents↗
PubMed1997

Double-blind, randomized comparison of itraconazole capsules vs. placebo in the treatment of toenail onychomycosis.

Three multicenter, randomized, double-blind, placebo-controlled studies were conducted to determine whether twelve weeks of therapy with itraconazole, 200 mg, was effective in the treatment of dermatophyte infection of the toenail. Significantly more patients treated with itraconazole (110 patients) than with placebo (104 patients) achieved clinical (65 percent vs. 3 percent) and mycologic (54 percent vs. 6 percent) success. The mean percentage of affected reference nail before the initiation of therapy was 76 percent. Adverse events were comparable in the two treatment groups. These findings demonstrate that twelve weeks of continuous itraconazole, 200 mg once daily, is a highly effective, well-tolerated therapy for the management of toenail onychomycosis.

Adolescent↗
PubMed1996

Onychomycosis: a significant medical disorder.

A number of factors have contributed to the growing incidence of fungal nail infections, including an aging population, an expanding number of immunocompromised patients, and increasing participation in fitness-related activities. Although onychomycosis and other nail diseases can adversely affect the appearance of the nail unit, the impact of such nail disfigurement extends well beyond the aesthetic realm. In fact, many patients with fungal nail infections experience serious physical, psychosocial, and occupational effects as a result of this disease. In addition, onychomycosis is a serious health burden, particularly in older persons, and has a major economic impact on the healthcare system.

AIDS-Related Opportunistic Infections↗
PubMed1996

Newer systemic antifungal drugs for the treatment of onychomycosis.

Onychomycosis, the infection of the nail unit by any fungus, far from being just a cosmetic problem, has significant psychological, physical, social, and financial implications. Further, it has experienced a dramatic rise in incidence in recent years. The introduction of newer systemic antifungal drugs (itraconazole, fluconazole, and terbinafine) offer an increased cure rate, a broader spectrum of activity, shortening of the treatment period, and increased safety, compared with the traditional systemic antifungal drugs griseofulvin and ketoconazole. Because the fungi involved are difficult to eradicate from the floors of communal bathing facilities, where the infection is often contracted, an effective treatment is likely to have a significant impact on disease prevalence.

Aged↗