RESUMO
BACKGROUND: The prevalence of superficial fungal infections in India is believed to have increased substantially in the past decade. We evaluated the treatment outcomes and risk factors associated with clinical response to a treatment course of itraconazole for the management of dermatomycosis in India. METHODS: In this real-world, prospective pilot study (August 2019 to March 2020), adult participants (18-60 years), diagnosed with T. cruris or T. corporis, received itraconazole 200 mg/day (any formulation) orally for 7 days, and were followed for an additional 7 days. RESULTS: The study was terminated early due to the COVID-19 pandemic. Of 40 enrolled participants (mean [SD] age, 35.5 [12.73] years; {62.5%}] male; 37 received itraconazole and 20 (50%) completed the study. The median (range) Clinical Evaluation Tool Signs and Symptoms total score at baseline was 5.5 (2-10). Clinical response of "healed" or "markedly improved" based on the Investigator Global Evaluation Tool at day 7 (primary objective) was 42.9% (12/28; 95% CI: 24.53%, 61.19%). Itraconazole minimum inhibitory concentration for identified microorganisms, T. mentagrophytes species complex (91.7%) and T. rubrum (8.3%), was within the susceptibility range (0.015-0.25 mcg/mL). At day 14, 8/13 (61.5%) participants achieved a mycological response, 2/13 participants (15.4%) had a mycological failure and 90% showed a clinical response. CONCLUSION: COVID-19 pandemic affected patient recruitment and follow-up, so the findings call for a careful interpretation. Nevertheless, this real-world study reconfirmed the clinical efficacy and microbial susceptibility to itraconazole for the fungi causing dermatophytosis in India. TRIAL REGISTRATION: Trial registration number: Clinicaltrials.gov NCT03923010.
Assuntos
COVID-19 , Dermatomicoses , Tinha , Adulto , Masculino , Humanos , Itraconazol/farmacologia , Antifúngicos/farmacologia , Tinha/induzido quimicamente , Tinha/tratamento farmacológico , Tinha/microbiologia , Projetos Piloto , Estudos Prospectivos , PandemiasRESUMO
BACKGROUND AND DESIGN: In the treatment of onychomycosis, oral therapies have generally been given as a continuous-dosing regimen. For example, the suggested dose of itraconazole for the treatment of onychomycosis has thus far been 200 mg/d for 3 months. Based on the advances in our understanding of the pharmacokinetics of itraconazole, we investigated the efficacy and nail kinetics of intermittent pulse-dosing therapy with oral itraconazole in patients who were suffering from onychomycosis. Fifty patients with confirmed onychomycosis of the toenails, predominantly Trichophyton rubrum, were recruited and randomly assigned to three (n = 25) or four (n = 25) pulses of 1-week itraconazole therapy (200 mg twice daily for each month). Clinical and mycological evaluation of the infected toenails, and determination of the drug levels in the distal nail ends of the fingernails and toenails, were performed at the end of each month up to month 6 and then every 2 months up to 1 year. RESULTS: In the three-pulse treatment group, the mean concentration of itraconazole in the distal ends of the toenails ranged from 67 (month 1) to 471 (month 6) ng/g, and in the distal ends of the fingernails, it ranged from 103 (month 1) to 424 (month 6) ng/g. At month 11, the drug was still present in the distal ends of the toenails at an average concentration of 186 ng/g. The highest individual concentrations of 1064 and 1166 ng/g were reached at month 6 for toenails and fingernails, respectively. At end-point follow-up, toenails in 84% of the patients were clinically cured with a negative potassium hydroxide preparation and culture in 72% and 80% of the patients, respectively. In the four-pulse treatment group, the mean concentration of itraconazole in the distal ends of the toenails ranged from 32 (month 1) to 623 (month 8) ng/g, and in the distal ends of the fingernails, it ranged from 42 (month 1) to 380 (month 6) ng/g. The highest individual concentrations of 1549 and 946 ng/g were reached at month 7 for toenails and at month 9 for fingernails, respectively. At month 12, the drug was still present in the distal ends of the toenails at an average concentration of 196 ng/g. At end-point follow-up, toenails in 76% of the patients were clinically cured with a negative potassium hydroxide preparation and culture in 72% and 80% of the patients, respectively. There were no significant intergroup differences between the three- and four-pulse treatment groups for the primary efficacy parameters. The drug was well tolerated with no significant side effects in either patient group. CONCLUSIONS: Following pulse therapy with itraconazole (400 mg/d given for 1 week each month for 3 to 4 months), the drug has been detected in the distal ends of nails after the first pulse, and it has reached therapeutic concentrations with further therapy. After stopping the last pulse, the drug remains in the nail plate at levels above 300 ng/g for several months. Clinical cure rates between 76% and 84% and negative mycological examination findings between 72% and 80%, respectively, were observed in toenail onychomycosis. The data suggest that pulse therapy with itraconazole is an effective and safe treatment option for onychomycosis.
Assuntos
Antifúngicos/administração & dosagem , Itraconazol/administração & dosagem , Onicomicose/tratamento farmacológico , Idoso , Análise de Variância , Antifúngicos/farmacocinética , Distribuição de Qui-Quadrado , Esquema de Medicação , Feminino , Seguimentos , Dermatoses do Pé/tratamento farmacológico , Dermatoses do Pé/metabolismo , Dermatoses do Pé/microbiologia , Dermatoses da Mão/tratamento farmacológico , Dermatoses da Mão/metabolismo , Dermatoses da Mão/microbiologia , Humanos , Itraconazol/farmacocinética , Masculino , Unhas/metabolismo , Unhas/microbiologia , Onicomicose/metabolismo , Onicomicose/microbiologia , Trichophyton/isolamento & purificaçãoRESUMO
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.
Assuntos
Onicomicose/tratamento farmacológico , Antifúngicos/administração & dosagem , Antifúngicos/uso terapêutico , Ensaios Clínicos como Assunto , Estudos de Avaliação como Assunto , Dermatoses do Pé , Dermatoses da Mão , Humanos , Onicomicose/etiologia , Onicomicose/fisiopatologiaRESUMO
In an open study, twenty-eight patients with toenail onychomycosis were treated with monthly cycles of 400 mg itraconazole daily for one week for three (n = 5) or four (n = 23) consecutive months. In this patient sample, a total of seventy-one toenails were affected, with a mean nail-plate involvement of 55 percent (range, 20 to 100 percent). Trichophyton rubrum was the most frequently isolated pathogen, followed by T. mentagrophytes. After active therapy, patients were evaluated for a maximum period of two years (mean, twelve months). A total of twenty-six of twenty-eight patients (93 percent) were considered as clinically cured. Of the remaining two patients, one was markedly improved and one appeared to have relapsed. Only three of seventy-one nails still exhibited some pathologic involvement. Of the twenty-six patients considered cured, mycologic examination at the final visit was performed on thirteen and the results were negative in all of them. The remaining clinically cured patients had no mycologic examination at the last visit. This short treatment was well tolerated; the only adverse reaction being a mild headache in one patient. Patients preferred this regimen to receiving daily treatment for three months. Pulse therapy consisting of monthly one-week cycles of 400 mg itraconazole daily for three to four months may offer a new option for treatment of onychomycosis. Further large-scale studies are required to confirm these findings.
Assuntos
Antifúngicos/uso terapêutico , Itraconazol/uso terapêutico , Onicomicose/tratamento farmacológico , Adulto , Idoso , Antifúngicos/administração & dosagem , Esquema de Medicação , Feminino , Dermatoses do Pé/tratamento farmacológico , Humanos , Itraconazol/administração & dosagem , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
Pityriasis capitis is improved by the use of antifungal shampoos. A double-blind randomized, placebo-controlled study was conducted to compare the efficacy of ketoconazole 0.5 percent and 1 percent formulation shampoos. Evaluations were made in seventy-eight volunteers before and after a two-week duration of daily shampooing. Grading the Malassezia ovalis load in dandruff and values of squamometry were used as noninvasive methods to evaluate efficacy.
Assuntos
Preparações para Cabelo , Cetoconazol/administração & dosagem , Malassezia/isolamento & purificação , Pitiríase/tratamento farmacológico , Dermatoses do Couro Cabeludo/tratamento farmacológico , Adolescente , Adulto , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pitiríase/microbiologiaRESUMO
This paper compares the antifungal activity and efficacy of itraconazole and terbinafine in vitro with their experimental activity and efficacy in vivo in patients with superficial fungal infections (tinea pedis and onychomycosis). Onychomycosis and tinea pedis are often treated with oral antifungals. With the introduction of newer agents, such as terbinafine and itraconazole, efficacy and safety have been improved. In vitro evaluation showed somewhat better results for terbinafine over itraconazole against dermatophytes, but in vivo results were at least equivalent. Moreover, according to ex vivo studies, itraconazole is a broad-spectrum agent with higher cure rates than terbinafine for fungal infections other than dermatophytosis (e.g., Candida infections). A meta-analysis of data from all published clinical trials comparing the efficacy and safety of terbinafine and itraconazole revealed similar high cure rates (> 70%) for both antifungal agents and similar adverse-event profiles. Both treatments were safe and well tolerated. Antifungal research has responded to the challenges of treating superficial infections by developing effective, well-tolerated, fast-acting antifungal therapies. The reduction in treatment duration also has led to improved patient compliance. The most notable difference between itraconazole and terbinafine is the 1-week pulse regimen available with itraconazole as opposed to the continuous treatment course available for terbinafine.
Assuntos
Antifúngicos/uso terapêutico , Itraconazol/uso terapêutico , Naftalenos/uso terapêutico , Onicomicose/tratamento farmacológico , Tinha dos Pés/tratamento farmacológico , Administração Oral , Animais , Antifúngicos/farmacologia , Humanos , Itraconazol/farmacologia , Naftalenos/farmacologia , TerbinafinaRESUMO
After experience with more than 34 million patients over 10 years, the safety of itraconazole and its potential drug-drug interactions are well known. In clinical trials, the average incidence of adverse events with a 1-week pulse regimen was 18% in pooled safety data (n = 2,867); only 2.2% of patients dropped out. In direct comparative trials, the incidence of mild and reversible adverse effects was comparable for itraconazole and terbinafine (31% and 28%, respectively) during treatment. The rate of permanent withdrawal because of adverse events was 3.6% for itraconazole and 7.5% for terbinafine (P < .05). Itraconazole was significantly better tolerated as evaluated by the investigator and patients. The analysis of the elderly subpopulation showed that patients 65 and older tolerated itraconazole pulse well, with only 20% experiencing mild and reversible side effects (total group). In direct comparative trials, itraconazole also produced fewer adverse effects than terbinafine (13% vs 32%, respectively). As newer oral antifungal agents gain widespread use, clinicians need to be aware of their potential drug-drug interactions and their possibly serious adverse events. However, pooled data from the 1-week itraconazole pulse regimen indicated a favorable safety profile, and a dose increase to 400 mg had no impact on safety.
Assuntos
Antifúngicos/efeitos adversos , Itraconazol/efeitos adversos , Onicomicose/tratamento farmacológico , Idoso , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Esquema de Medicação , Feminino , Humanos , Itraconazol/farmacologia , Itraconazol/uso terapêutico , Testes de Função Hepática , Naftalenos/efeitos adversos , Naftalenos/uso terapêutico , Gravidez , TerbinafinaAssuntos
Imidazóis/uso terapêutico , Ceratose/tratamento farmacológico , Inibidores de Lipoxigenase/uso terapêutico , Piperazinas/uso terapêutico , Adolescente , Adulto , Araquidonato 5-Lipoxigenase , Feminino , Humanos , Imidazóis/administração & dosagem , Lactente , Inibidores de Lipoxigenase/administração & dosagem , Masculino , Pessoa de Meia-Idade , Pomadas , Piperazinas/administração & dosagemRESUMO
OBJECTIVE: To compare the antifungal activity of itraconazole and terbinafine in vitro and to relate them to their experimental in vivo activity and to their efficacy in patients with superficial fungal infections (tinea pedis and onychomycosis). RESULTS: Fungal infections such as onychomycosis and tinea pedis are often treated with oral antifungals. With the introduction of newer agents such as terbinafine and itraconazole, efficacy and safety have been improved. In vitro evaluation showed somewhat better results against dermatophytes for terbinafine than for itraconazole, but in vivo results were at least equivalent. Moreover, itraconazole is a broad-spectrum agent with higher cure rates for infections other than dermatophytosis (e.g. for Candida infections) than terbinafine, according to ex vivo studies. A review of all published clinical trials, comparing the efficacy and safety of terbinafine and itraconazole in a meta-analysis revealed similar and high cure rates (>70%) for both antifungal agents and similar adverse event profiles. Both treatments were safe and well tolerated. CONCLUSIONS: Antifungal research has responded to the challenges of treating superficial infections by developing effective, well-tolerated, fast-acting antifungal therapies. The reduction in treatment duration has also led to improved patient's compliance. The most noticeable difference between itraconazole and terbinafine is the 1-week pulse concept of itraconazole in contrast to the continuous treatment concept of terbinafine.
Assuntos
Antifúngicos/uso terapêutico , Dermatoses do Pé/tratamento farmacológico , Itraconazol/uso terapêutico , Naftalenos/uso terapêutico , Animais , Antifúngicos/farmacologia , Ensaios Clínicos como Assunto , Humanos , Técnicas In Vitro , Itraconazol/farmacologia , Naftalenos/farmacologia , Onicomicose/tratamento farmacológico , Terbinafina , Tinha dos Pés/tratamento farmacológicoRESUMO
The purpose of this article is to review the pharmacologic properties of two newer agents, itraconazole and terbinafine, and to assess their clinical efficacy in onychomycosis. Both drugs are effective in treating infections caused by dermatophytes. Itraconazole appears to be more efficacious in infections caused by Candida species. The improved effectiveness of these agents is probably related to their rapid penetration into the nails and prolonged bioavailability at the site of infection.
Assuntos
Antifúngicos/uso terapêutico , Cetoconazol/análogos & derivados , Naftalenos/uso terapêutico , Onicomicose/tratamento farmacológico , Adulto , Humanos , Itraconazol , Cetoconazol/uso terapêutico , Masculino , TerbinafinaRESUMO
Initial dose-finding and placebo-controlled studies in skin dermatophytoses demonstrated that itraconazole was more effective than placebo and that short-term treatment with itraconazole 100 mg daily gave better results than 50 mg daily. Subsequently, an approach has been followed which is quite different from the classical attitude in treating fungal infections. Indeed, it is usual policy to continue antifungal therapy for some days after complete disappearance of clinical signs and symptoms. With itraconazole, the opposite approach has been followed. Kinetic studies have shown that (a) tissue levels are higher (up to ten times in skin areas with a high density of sebaceous glands) than corresponding plasma levels, and (b) therapeutic concentrations of itraconazole remain present in the epidermis for up to four weeks after discontinuation of therapy, plasma levels being undetectable after one week. These findings confirm the exceptional affinity of itraconazole for the epidermis without re-uptake into the blood circulation. Based on these findings, fixed treatment schedules were initiated with a 15-day treatment course of 100 mg itraconazole once daily in patients with tinea cruris, tinea corporis or tinea pedis, with a 30-day treatment of 100 mg itraconazole once daily in patients with palmoplantar infections. With these short and fixed treatment regimens it became evident that an 80% mycological cure and a 90% clinical response could be obtained 3-4 weeks after discontinuation of therapy in tinea corporis/cruris infections when itraconazole was given at a daily dose of 100 mg for 15 days.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Antifúngicos/uso terapêutico , Dermatomicoses/tratamento farmacológico , Cetoconazol/análogos & derivados , Humanos , Itraconazol , Cetoconazol/uso terapêuticoRESUMO
The efficacy and safety of an intermittent itraconazole dosing regimen was investigated in 354 patients with toenail onychomycosis, from 98 dermatology centres. Patients received itraconazole 400 mg daily for 1 week per month for 3 months. If the nail of the big toe was completely involved, a fourth treatment cycle was administered. Because of the short-term nature of the dosing regimen, renal and liver function tests were not compulsory. Cure rates were influenced by proximal nail involvement, particularly in the big toenails. At the end of month 10, clinical cure (complete clearance or clearance with a few small residual lesions) was achieved in 64% of patients with proximal nail involvement in the big toenails, in 77% of patients with proximal nail involvement in other toenails and in 87% of patients without proximal nail involvement; mycological cure was achieved in 77% of 197 patients examined. Fifty-nine patients (17%) reported adverse events: mainly headache, fatigue or minor gastrointestinal problems; only nine patients (3%) stopped treatment because of adverse events. Response rates were similar to those achieved with 3 months of continuous therapy with itraconazole or terbinafine but intermittent therapy is probably safer and is considerably cheaper than continuous itraconazole treatment.
Assuntos
Antifúngicos/administração & dosagem , Dermatoses do Pé/tratamento farmacológico , Itraconazol/administração & dosagem , Onicomicose/tratamento farmacológico , Administração Oral , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cooperação do Paciente , Resultado do TratamentoRESUMO
In this open label, multicentre trial, 44 patients with clinical and mycological evidence of Candida onychomycosis were treated with itraconazole pulse therapy. Onychomycosis of the toes alone and concomitant disease involving the fingers and toes was treated with three pulses, and onychomycosis of the fingers alone with two pulses. Final evaluation for patients with finger and toe onychomycosis was at 6-9 months and 9-12 months, respectively. There were 29 patients with toe onychomycosis (C. albicans, 27; C. glabrata, one; Candida species, one), 12 patients with finger onychomycosis (C. albicans, two; C. glabrata, one) and three patients had combined toe and finger onychomycosis (C. albicans, two; C. guillermondii, one). In the patients with toe onychomycosis mycological cure was observed in 29 of 32 patients (90.6%). There was complete cure [mycological cure (negative culture and KOH at endpoint evaluation) with clinical cure] or marked improvement (mycological cure with 75% or greater decrease in area of involvement of target nail compared with pretherapy) in 24 of 32 patients (75.0%). All 12 patients with finger onychomycosis alone due to Candida species achieved a mycological cure (100%). In this group of patients complete cure or marked improvement was observed in 11 of 12 patients (91.7%). Itraconazole pulse therapy was well tolerated and no serious adverse events were reported in the patients treated with this triazole. In conclusion, itraconazole pulse therapy is an effective and safe treatment for both finger and toe onychomycosis associated with Candida.
Assuntos
Antifúngicos/administração & dosagem , Candidíase/tratamento farmacológico , Itraconazol/administração & dosagem , Onicomicose/tratamento farmacológico , Adulto , Idoso , Candidíase/diagnóstico , Relação Dose-Resposta a Droga , Feminino , Seguimentos , Dermatoses do Pé/tratamento farmacológico , Dermatoses da Mão/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Onicomicose/diagnóstico , Pulsoterapia , Resultado do TratamentoRESUMO
We describe the case of a female patient suffering from yellow nail syndrome (YNS) accompanied by bronchial hyperactivity and sinusitis. A dermatophyte onychomycosis was evident on some of her nails. Following treatment of the respiratory pathology and oral administration of vitamin E, there was an improvement in the nails. The improvement of the yellow nails was however more discernible subsequent to the introduction of itraconazole pulse therapy for secondary onychomycosis suggesting an effect of this treatment on ungual growth.
Assuntos
Doenças da Unha/complicações , Onicomicose/complicações , Transtornos da Pigmentação/complicações , Adulto , Antifúngicos/uso terapêutico , Broncopatias/complicações , Quimioterapia Combinada , Feminino , Humanos , Itraconazol/uso terapêutico , Doenças da Unha/tratamento farmacológico , Onicomicose/tratamento farmacológico , Transtornos da Pigmentação/tratamento farmacológico , Sinusite/complicações , Síndrome , Vitamina E/uso terapêuticoRESUMO
Prevention of athlete's foot is a difficult problem. Using non-invasive biometrological methods, we evaluated the changes induced in the stratum corneum by a 3-week treatment with miconazole spray powder. A total of 16 athletes apparently at risk of developing tinea pedis, but without any evidence for the disease at the time of inclusion, participated in the study. They applied the medicated powder to one foot daily, while the other foot remained untreated to serve as a control. No adverse events occurred. In comparison with the control site, the capacitance of the toeweb skin was significantly reduced by the treatment. The ex vivo bioassay of dermatophyte culture on stratum corneum demonstrated a significant inhibition of growth of Trichophyton mentagrophytes var. interdigital at the treated site. The results of this study provide indirect evidence that the regular use of miconazole spray powder decreases the risk of developing athlete's foot.
Assuntos
Antifúngicos/uso terapêutico , Miconazol/uso terapêutico , Tinha dos Pés/prevenção & controle , Adulto , Resposta Galvânica da Pele , Humanos , Masculino , Trichophyton/efeitos dos fármacos , Trichophyton/crescimento & desenvolvimentoRESUMO
BACKGROUND: In recent years, itraconazole pulse therapy for onychomycosis has been developed [three 1-week pulses with itraconazole 400 (2 x 200) mg daily every month]. This has proved an effective and safe regimen which requires only 50% of the medication used for continuous dosing schedules. Parallel to the development of the new dosage schedule, additional studies were conducted to further document the safety and efficacy of itraconazole 200 mg once daily for 3 months to treat onychomycosis. OBJECTIVE: To compare the safety of itraconazole 200 mg once daily for 3 months, with or without itraconazole 200 mg once weekly for a further 3 months, with that of miconazole cream twice daily for 6 months, in the treatment of onychomycosis. Treatment efficacy was compared as a secondary objective. METHODS: In this multicenter, double-blind study, patients were randomized to receive itraconazole 200 mg once daily for 3 months followed by either itraconazole 200 mg once weekly for 3 months (ITR-ITR group, n = 599) or oral placebo once weekly for 3 months (ITR-PLAC group, n = 613), or to receive miconazole cream twice daily for 6 months (MIC-MIC group, n = 396). The primary variable was elevation of alanine amino-transferase (ALT) concentration above 50 U/I. RESULTS: Overall incidence of elevation of ALT concentration above 50 U/I, adverse events and rate of withdrawal because of adverse events were low and similar in the three treatment groups. Efficacy was significantly greater in the ITR groups than the MIC-MIC group. CONCLUSION: Itraconazole and miconazole were well tolerated and had no significant effect on liver function, but itraconazole was significantly more effective.
Assuntos
Antifúngicos/uso terapêutico , Itraconazol/uso terapêutico , Miconazol/uso terapêutico , Onicomicose/tratamento farmacológico , Administração Oral , Adulto , Idoso , Método Duplo-Cego , Feminino , Dermatoses do Pé/tratamento farmacológico , Alemanha , Dermatoses da Mão/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
BACKGROUND: The evaluation of antifungal agents by in vitro and animal experiments cannot predict clinical efficacy with certainty. New models are needed to assess and compare antifungal activity. OBJECTIVE: We compared on human stratum corneum ex vivo the antifungal activity and lingering effect of 200 mg itraconazole daily and twice daily, and 250 mg/day terbinafine. METHODS: Three groups of 10 healthy volunteers entered the open comparative trial. Results were evaluated in a blinded manner. Cyanoacrylate skin surface strippings (CSSS) were taken from the back and superficial dermatome skin samples (SDSS) were taken from plantar skin at days 0, 1, 3, 7, 8, 10, 14, 21, 28, and 35. Spores or yeasts of selected fungi (Trichophyton rubrum, Trichophyton mentagrophytes, Microsporum canis, and Candida albicans) were deposited and cultured on the CSSS and SDSS. The 1-week fungal growth on CSSS and SDSS was assessed over time by computerized image analysis to derive the inhibitory effect of the oral antifungal agents administered. Fungitoxic activity was also assessed by the use of 2-day cultures on CSSS followed by a transfer to Sabouraud medium. RESULTS: Comparable antifungal activity against dermatophytes was found for all three regimens. Itraconazole at both dosages was always significantly more active than terbinafine against C. albicans on CSSS and SDSS. Overall, 200 mg itraconazole twice daily appeared to be more fungitoxic than 250 mg/day terbinafine and 200 mg/day itraconazole. CONCLUSION: The ex vivo culture of fungi on human stratum corneum is very similar to the in vivo situation. Both itraconazole and terbinafine display high antidermatophyte activity. Faster onset and longer posttherapy activity were demonstrated in the itraconazole treatment groups. Terbinafine had marginal activity against C. albicans in this model.
Assuntos
Antifúngicos/uso terapêutico , Dermatomicoses/tratamento farmacológico , Itraconazol/uso terapêutico , Naftalenos/uso terapêutico , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Método Simples-Cego , TerbinafinaRESUMO
Itraconazole 5 mg/kg/day given as pulse therapy, each of 1 week duration, for 1 to 3 pulses appears to be an effective and safe method of treating tinea capitis. The number of pulses of therapy may depend upon several factors, including the severity of disease and area of involvement. Controlled studies are needed to determine the number of pulses of itraconazole required to treat tinea capitis.
Assuntos
Antifúngicos/administração & dosagem , Itraconazol/administração & dosagem , Tinha do Couro Cabeludo/tratamento farmacológico , Criança , Pré-Escolar , Esquema de Medicação , Seguimentos , Humanos , MasculinoRESUMO
Recently the pharmacologic role of leukotrienes (LTs), especially that of LTB4, has been intensively investigated in psoriasis. In vitro, R 68 151 is a potent 5-lipoxygenase inhibitor and consequently reduces LTB4 formation. Therefore the role of an in vitro 5-lipoxygenase inhibitor and its clinical use in psoriasis were evaluated with topical R 68 151 in a double-blind vehicle-controlled study. Eighty-eight patients with localized psoriatic lesions were treated twice daily with R 68 151 2% ointment (n = 44) or vehicle ointment (n = 44) during 4 weeks. Most patients (n = 73) had psoriasis vulgaris (n = 37, R 68 151; n = 36, vehicle). In 27% of the R 68 151-treated patients with psoriasis vulgaris, the lesions disappeared or showed marked improvement, compared with 8% in the vehicle group (X2, p = 0.06). The scores in global evaluation, however, were significantly different between both treatment groups (p less than 0.05, Mann-Whitney U test). The improvement of the mean symptom score with R 68 151 was 46% for scaling and 34% for erythema at the end of the study compared with an improvement of 6% and a deterioration of 3%, respectively, in the control group (p less than 0.05, p less than 0.01; Mann-Whitney U test). The global evaluation in the total group of patients with psoriasis (all different subtypes) was consistent with the response rate in the group of patients with psoriasis vulgaris: 30% in the test group versus 11% in the control group (X2, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Araquidonato Lipoxigenases/antagonistas & inibidores , Imidazóis , Inibidores de Lipoxigenase , Piperazinas , Psoríase/tratamento farmacológico , Administração Cutânea , Adolescente , Adulto , Idoso , Araquidonato 5-Lipoxigenase/administração & dosagem , Araquidonato 5-Lipoxigenase/efeitos adversos , Araquidonato 5-Lipoxigenase/uso terapêutico , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Veículos FarmacêuticosRESUMO
Keratinocyte growth in vitro and DNA synthesis by epidermal cells in vivo are inhibited by therapeutic doses of cyclosporin A (CsA). This effect may be potentialized by topical treatment with ketoconazole, since this drug has been shown to inhibit CsA metabolism. Normal human skin grafts on nude mice receiving intraperitoneal injections of CsA were treated with ketoconazole cream or its placebo for 3 weeks. The keratinocyte DNA synthesis rate was evaluated through the rates of bromodeoxyuridine (BrdU) incorporation, and the trough blood levels of CsA were checked at the end of the experiment. Counting of the BrdU-labelled nuclei in human tissue sections confirmed a dose-dependent inhibition of BrdU incorporation by keratinocytes exposed to CsA. This CsA-induced inhibition was further increased in the animals treated with ketoconazole cream. This effect was best seen in the groups treated with the low-to-medium doses of CsA (12.5 and 25 mg/kg/day). However, the simultaneous increase in the circulating CsA levels was also observed in these animals. Based on our results, we speculate that the potentializing effect of ketoconazole on CsA-induced inhibition of keratinocyte DNA synthesis is systemic rather than local.