伊曲康唑间歇冲击疗法治疗甲真菌病的血清及甲中药物水平的研究

目的 了解伊曲康唑间歇冲击疗法治疗甲真菌病的血清及甲中药物水平的变化,为该疗法提供药物动力学依据。方法 １５例趾甲真菌病患者经伊曲康唑间歇冲击疗法治疗;于服药前、服药后每月取患者血清（共３月）并收集远端甲标本,将指甲和趾甲分开;以高效液相色谱（ＨＰＬＣ）测定伊曲康唑的含量。结果 １．每次冲击后４周,血清中均未测得伊曲康唑;２．甲组织中伊曲康唑水平较高,在２或３月时达到高峰;３．停药后,伊曲康唑仍能以较高的水平在甲中存在至６月后;同一时间点,指甲和趾甲中的药物水平无统计学差异（Ｐ〉０．０５）。结论 伊曲康唑经口服吸收后从血液迅速向甲组织分布,停药后,以较高水平在甲组织中持续存在６月以上。     

伊曲康唑和特比萘芬序贯法治疗甲真菌病疗效观察

目的观察伊曲康唑和特比萘芬序贯疗法治疗甲真菌病的临床疗效及安全性。方法对照组采用伊曲康唑冲击治疗(每日中晚餐各口服伊曲康唑200mg,连用1周,停用3周为一个疗程),指甲真菌病治疗2个疗程,趾甲真菌病治疗3个疗程。观察组指甲真菌病先用伊曲康唑冲击治疗1个疗程,随后应用盐酸特比萘芬冲击疗法(每日中晚餐各口服特比萘芬250mg,连用1周,停药3周),趾甲真菌病还需再重复伊曲康唑冲击治疗1个疗程。两组治疗结束后3、6月时各复诊一次,观察不良反应发生情况。结果观察组治疗3个月后的有效率显著高于对照组(P0.05),经6个月治疗后,2组有效率与治疗3个月后有效率相比均略有提高,但差异无统计学意义(P0.05),观察组有效率高于对照组,但无显著性差异(P0.05)。复发率观察显著低于对照组(P0.05)。结论伊曲康唑和特比萘芬序贯疗法治疗甲真菌病疗效确切,复发率与不良反应较少,值得临床推广应用。     

伊曲康唑间隙冲击疗法治疗甲真菌病200例

目的 :观察伊曲康唑冲击疗法治疗甲真菌病的临床疗效。方法 :2 0 0例甲真菌病患者每天口服伊曲康唑胶囊 2次 ,每次 2 0 0mg× 7天 ,停药 2 1天为 1个疗程。指甲真菌病用药 2个疗程 ,趾甲真菌病及指趾甲真菌病用药 3个疗程。结果 82例指甲真菌病临床痊愈率 91 4 6 % ,118例趾甲真菌病及指趾甲同患真菌病临床痊愈率 81 36 % ,二者伴发皮肤真菌感染者真菌清除率分别为 98 5 %和 97%。结论 :伊曲康唑短期冲击疗法治疗甲真菌病疗程短、疗效高、副作用小、安全性高、复发率低。     

伊曲康唑间隙冲击疗法治疗甲真菌病

观察伊曲康唑间隙冲击疗法治疗甲真菌病的临床疗效。182例甲真菌病患者每天口服伊曲康唑胶囊2次,每次200mg×7天,停药21天为1疗程。指甲真菌病用药2个疗程,趾甲真菌病及指趾甲真菌病用药3个疗程。结果55例指甲真菌病临床痊愈率90.9%,127例趾甲真菌病及指趾甲同患真菌病临床痊愈率80.3%,二者伴发皮肤真菌感染者真菌清除率分别为98%和96.5%。     

伊曲康唑和特比萘芬序贯疗法治疗甲真菌病的临床观察

目的:探讨序贯疗法治疗甲真菌病的安全性、依从性和疗效.方法:甲真菌病患者先服伊曲康唑1周,停3周为1个疗程,接着服特比萘芬1周,停3周为1个疗程.指甲真菌病服2个疗程,趾甲真菌病服3个疗程.结果:指甲真菌病有效率100%,趾甲真菌病有效率90.91%.结论:伊曲康唑与特比萘序贯疗法治疗甲真菌病安全有效,依从性好.     

国产伊曲康唑分散片间隙冲击治疗甲真菌病多中心对照研究

目的:评价国产伊曲康唑分散片间隙冲击疗法治疗甲真菌病的疗效和安全性.方法:采用多中心、阳性药物平行对照的临床研究.试验组和对照组分别接受国产伊曲康唑分散片和进口伊曲康唑胶囊口服治疗.在治疗前、治疗后分别对各观察指标进行记录、分析和评估.结果:共入选病例186 例,完成试验178 例,其中试验组90 例,对照组88 例.试验组和对照组指甲真菌病治疗第9 、12 、24 周有效率分别为68.76% 、90.63% 、96.88% 和66.66% 、88.89% 、96.30% ;试验组和对照组趾甲真菌病第13 、24 、36 周有效率分别为62.07% 、93.11% 、94.83% 和60.65% 、91.81% 、95.08%.两组对应观察期有效率经卡方检验,差异无统计学意义.治疗开始至观察期结束两组均未出现严重药物相关不良事件,治疗期间试验组出现2 例服药后轻微消化道反应,3 例转氨酶轻度升高,1 例尿蛋白阳性;对照组出现3 例服药后轻微消化道反应,2 例转氨酶轻度升高,所有患者治疗结束后均恢复正常.两组不良反应发生率差异无统计学意义.结论:国产伊曲康唑分散片治疗甲真菌病疗效和安全性与进口伊曲康唑胶囊相当.     

伊曲康唑治疗甲真菌病32例

目的　分析伊曲康唑的作用机理 ,进而探索甲真菌病安全有效的治疗方法。方法　 3 2例甲真菌病患者采用伊曲康唑口服治疗 ,每日早晚脂餐送服伊曲康唑 0 .2g ,每月服药 1周 ,停 3周 ,连服 4月后停药观察。结果　 3 2例患者痊愈 2 7例 ,显效 2例 ,有效 2例 ,无效 1例 ,治愈率 84.3 8% ,有效率 96.88% ,真菌清除率 84.3 8%。结论　口服伊曲康唑治疗甲真菌病疗效高 ,安全性好。     

伊曲康唑治疗足癣40例疗效观察

为了解口服伊曲康唑胶囊治疗足癣的疗效和安全性，采用开放性临床试验治疗40例足癣。伊曲康唑200mg，每日1次共7天，停药时有效率为35%，停药后4周有效率为97.5%，真菌清除率为62.5%。40例患者治疗后无不良反应，且耐受性好，伊曲康唑是治疗皮肤浅部真菌病安全有效的药物。     

甲真菌病临床评分指数指导伊曲康唑和特比萘芬治疗甲真菌病的疗效对比研究

目的评价甲真菌病临床评分指数(SCIO)指导伊曲康唑冲击和特比萘芬连续疗法治疗甲真菌病的疗效、安全性及费用疗效比。方法制定SCIO评分体系,对200例甲真菌病患者的靶甲进行SCIO评分,根据SCIO积分范围随机分为2组,分别给予伊曲康唑冲击治疗和特比萘芬连续治疗。结果2种药物均有较好的抗真菌疗效。伊曲康唑组和特比萘芬组近、中、远期临床和真菌学疗效差异均无统计学意义(P>0.05),伊曲康唑组远期复发率4.26%,特比萘芬组尚未观察到复发病例。伊曲康唑组不良事件发生率为23%,特比萘芬组为21%(P>0.05)。Ⅱ度患者伊曲康唑组费用疗效比低于特比萘芬组,Ⅲ度和Ⅳ度患者特比萘芬组费用疗效比低于伊曲康唑组,但差异均无统计学意义(P>0.05)。结论SCIO具有一定的科学性和实用性,指导伊曲康唑冲击和特比萘芬连续疗法治疗甲真菌病显示同样有效且安全。     

伊曲康唑与环吡酮联合治疗严重甲真菌病疗效观察

目的 :探讨口服伊曲康唑与外涂 8%环吡酮循序联合治疗严重甲真菌病的疗效及安全性。方法 :随机将 6 7例严重甲真菌病患者分为 2组 ,治疗组 35例 ,口服伊曲康唑间歇冲击与外涂 8%环吡酮甲涂剂循序联合治疗 ;对照组 32例 ,用 2 0 %乙酸溶液代替 8%环吡酮甲涂剂与伊曲康唑循序联合应用。结果 :在冲击治疗结束时 ,两组的治愈率、有效率及真菌转阴率没有差异。冲击治疗后 3月、6月及治疗结束后 3月 ,两组的临床总治愈率及有效率比较有显著性差异 (P <0 0 5 ) ,但真菌学阴转率比较无显著性差异 (P >0 0 5 )。结束治疗后 3个月时对照组临床复发 1例。结论 :口服伊曲康唑间歇冲击与外用 8%环吡酮甲涂剂联合治疗可作为严重甲真菌病首选方案之一。     

Continuous and intermittent itraconazole dosing schedules for the treatment of onychomycosis: a pharmacokinetic comparison

This multicentre, double-blind, randomized study compared the pharmacokinetics of itraconazole given at 200 mg once daily for 3 months and intermittently at 200 mg twice daily for 1 week per month followed by a 3-week drug-free period for 3 months in the treatment of onychomycosis. Patients were followed for 9 months after treatment. Itraconazole and hydroxy-itraconazole plasma concentrations and itraconazole nail tip concentrations were determined at regular intervals. With intermittent therapy (n = 64), increases of consistent magnitude were seen in the mean itraconazole and hydroxy-itraconazole plasma concentrations at the end of each 1-week treatment phase; values returned towards baseline during each subsequent 3-week drug-free period. The mean concentration of itraconazole in fingernail tips increased steadily from week 4, reached a maximum value at week 24 (213 ng/g), declined sharply between weeks 24 and 36 and returned to baseline by week 48; the mean concentration profile was similar for toenail tips (maximum value 305 ng/g at week 24) but decreased at a slower rate. With continuous therapy (n = 65), steady-state mean plasma concentrations of itraconazole and hydroxy-itraconazole were obtained within 4-5 weeks of the start of treatment and remained reasonably constant between weeks 4 and 12. The mean concentration of itraconazole in fingernail tips reached a maximum value at week 12 (524 ng/g) and returned towards baseline by week 48; in contrast, the maximum mean concentration of itraconazole in toenail tips was 698 ng/g at week 36 and did not return to baseline by week 48. No clear relationship was observed between response to treatment and concentration of itraconazole or hydroxy-itraconazole in plasma or itraconazole in nails, suggesting that concentrations exceeded therapeutic levels. In conclusion, intermittent therapy resulted in higher maximum itraconazole plasma concentrations but lower total drug exposure, and hence lower itraconazole nail concentrations, than continuous therapy. However, the intermittent schedule was not associated with a lower cure rate, which indicates that itraconazole nail concentrations remained within the therapeutic range.     

Pulse itraconazole vs. continuous terbinafine for the treatment of dermatophyte toenail onychomycosis in patients with diabetes mellitus

BACKGROUND: Oral terbinafine and oral itraconazole are two of the most common agents used for the treatment of toenail dermatophyte onychomycosis. Despite the fact that diabetic patients are more likely to have onychomycosis than normal individuals are, there is little research into the efficacy of standard oral regimens of terbinafine and itraconazole for onychomycosis in the diabetic population. STUDY DESIGN: We present a prospective, randomized, single-blind, parallel group, comparator-controlled, multi-centre study designed to assess the efficacy of the pulse itraconazole (200 mg twice daily, 1 week on, 3 weeks off, for 12 weeks) vs. continuous terbinafine (250 mg once daily for 12 weeks) oral therapies in the treatment of dermatophyte toenail distal and lateral subungual onychomycosis (DLSO) in the diabetic population. EFFICACY PARAMETERS: Primary efficacy measures included mycological cure rate (negative KOH and culture) and effective cure (mycological cure plus nail plate involvement of 10% or less) at Week 48. RESULTS: At Week 48, mycological cure was attained by 88.2% (30 of 34) and 79.3% (23 of 29) of patients in the itraconazole and terbinafine groups, respectively (P not significant). Effective cure (mycological cure with 相似文献   

Single-blind, randomized, prospective study on terbinafine and itraconazole for treatment of dermatophyte toenail onychomycosis in the elderly

BACKGROUND: The 2 most common agents used to treat dermatophyte onychomycosis of the toe are terbinafine (continuous) and itraconazole (pulse). Although comparative studies have been performed evaluating the efficacy of these 2 agents in adults, no such studies have been reported specifically in the elderly subset. OBJECTIVE: This prospective, randomized, single-blind, non--industry-sponsored, comparative study evaluated the efficacy and safety of terbinafine (continuous) and itraconazole (pulse) therapies in the treatment of dermatophyte onychomycosis of the toe in the elderly population. METHODS: Elderly patients (> or =60 years old) with dermatophyte onychomycosis of at least 1 great toe were randomly assigned to receive either terbinafine 250 mg/day for 12 weeks or itraconazole (pulse) 200 mg twice a day for 1 week, given for 3 pulses. At month 6 from the start of therapy, if there was less than 50% reduction in the affected nail plate area compared with baseline, or if there was less than 3 mm outgrowth of unaffected nail plate as measured in midline, then patients who had been administered terbinafine (continuous) therapy were given an extra 4 weeks of the drug (total of 16 weeks of therapy), and those who had received itraconazole (pulse) therapy were given an extra pulse (fourth pulse). Patients were evaluated at 1.5, 3, 6, 12, and 18 months from the start of therapy. The efficacy measures included mycologic cure rate and clinical efficacy (mycologic cure plus clinical cure or clinical improvement so that 10% or less of nail plate was clinically involved). RESULTS: There were 101 elderly patients enrolled in the study with 50 and 51 patients receiving terbinafine and itraconazole, respectively. The terbinafine group consisted of 28 men and 22 women, age (mean +/- standard error [SE]) 68.0 +/- 0.9 years, duration of onychomycosis (mean +/- SE) 18.2 +/- 1.4 years, number of nails involved (mean +/- SE) 5.5 +/- 0.5, and percent baseline nail plate area involved (mean +/- SE) 67.5% +/- 4.2%. The corresponding figures for the itraconazole (pulse) group were 24 men and 27 women, age (mean +/- SE) 68.8 +/- 0.8 years, duration of onychomycosis (mean +/- SE) 16.1 +/- 1.7 years, number of nails involved (mean +/- SE) 6.0 +/- 0.7, and percent baseline nail plate area involved (mean +/- SE) 74.9% +/- 3.8%, respectively, with no significant difference between the groups. At month 6, the number of patients that required an extra 4 weeks of terbinafine in the allylamine group or an extra itraconazole pulse in the triazole group was 13 of 50 and 23 of 51, respectively. The mycologic cure rate and clinical efficacy at 18 months from the start of therapy for the terbinafine group were 64.0% and 62.0%, respectively. The corresponding figures for the itraconazole (pulse) group were 62.7% and 60.8%, respectively, with no significant difference between the 2 groups. There were no dropouts during therapy. For both groups the drug appeared safe with no significant adverse events (AEs) or clinically significant laboratory abnormalities. All the AEs were mild and transient. There was high compliance with both regimens. CONCLUSIONS: In the elderly, for the treatment of dermatophyte toe onychomycosis, both terbinafine (continuous) and itraconazole (pulse) therapies are effective, safe, and associated with high compliance.     

Clinical and pharmacokinetic studies of continuous itraconazole for the treatment of onychomycosis

Itraconazole, a triazole antifungal agent, has been widely used for onychomycosis with high cure rates. Unchanged itraconazole and a major metabolite hydroxy-itraconazole reach the nail with a strong affinity for keratin. The aim of this study was to elucidate clinical effectiveness and pharmacokinetic profiles of a 6-month continuous itraconazole treatment at a daily dose of 100 mg. Nail growth, the decrease in nail turbidity, and the nail concentrations of unchanged- and hydroxy-itraconazole were investigated. The affected nails we examined demonstrated nail growth proportional to the decrease in turbidity and a quick increase in drug concentration with a long duration of a high concentration after cessation. Our results support the hypothesis that this continuous therapy is a good modality for onychomycosis.     

The significance of itraconazole for treatment of fungal infections of skin, nails and mucous membranes

Itraconazole is an antifungal drug from the triazole group with distinct in vitro activity against dermatophytes, yeasts and some molds. Itraconazole has a primarily fungistatic activity. Itraconazole accumulates in the stratum corneum and in nail material due to its high affinity to keratin, as well as in sebum and vaginal mucosa. Together with terbinafine and fluconazole, itraconazole belongs to the modern highly effective systemic antifungal drugs with a favorable risk-benefit ratio and for this reason is a preferred therapy option for fungal infections of skin, nails and mucous membranes. Compared to terbinafine in the treatment of fingernail and toenail fungal infections, itraconazole offers the advantage of a broad antifungal spectrum and better effectiveness against onychomycosis caused by yeasts yet appears inferior with regard to the more common dermatophyte infections. Itraconazole constitutes an important therapy option, along with fluconazole, terbinafine, ketoconazole and griseofulvin, for the treatment of dermatophyte infections of glabrous skin (tinea pedis, tinea manuum, tinea corporis and tinea cruris) in adults following unsuccessful topical therapy. In the oral therapy of tinea capitis, itraconazole plays an especially important role, in particular for disease caused by Microsporum canis (for children, however, only off-label use is feasible currently). In the treatment of oropharyngeal candidiasis, candidiasis of the skin and vulvovaginal candidiasis, itraconazole and fluconazole are the preferred treatment options in cases in which topical therapy has proven unsuccessful.     

An open randomized comparative study of oral itraconazole pulse and terbinafine pulse in the treatment of onychomycosis

BACKGROUND: Onychomycosis is a recalcitrant disease of the nails caused by dermatophytes, yeasts, and molds. AIMS: To compare the clinical efficacy of oral itraconazole pulse therapy and oral terbinafine pulse therapy in onychomycosis. METHODS: A randomized single-blind clinical comparative study was undertaken on 120 patients of onychomycosis during the period March 1999-February 2002. Sixty patients were randomly assigned to receive oral itraconazole 100 mg, two capsules twice daily for seven days a month and the other group of sixty patients received oral terbinafine 250 mg, one tablet twice daily for seven days every month. Four such monthly pulses were administered for each drug. The patients were evaluated at 4-weekly intervals till sixteen weeks and then at 24, 36 and 48 weeks. RESULTS: We observed a clinical cure rate of 82% and mycological cure rate of 90% in the group of patients treated with itraconazole while the group with terbinafine showed clinical and mycological cure rates of 79% and 87% respectively. This difference was not statistically significant. CONCLUSIONS: Both oral itraconazole and terbinafine are effective in the treatment of onychomycosis when administered in the pulse dosage form. Terbinafine is more cost effective while itraconazole has a broader spectrum of antimycotic activity.     

Therapeutic efficacy and safety of one-week intermittent therapy with itraconazole for onychomycosis in a Chinese patient population.

OBJECTIVE: To evaluate the efficacy and safety of a 1-week intermittent itraconazole dosing schedule for onychomycosis. METHODS: In this multicenter, open-label study, 646 patients received itraconazole 200 mg twice daily for 1 week/month, followed by 3 weeks without therapy. Patients with fingernail infections received 2 treatment cycles, patients with toenail or combined toenail and fingernail infections received 3 cycles. Efficacy was evaluated at week 9 (2-month regimen), week 13 (3-month regimen) and 3, 6 or 9 (toenails only) months after completion of therapy. RESULTS: Clinical and mycologic cure rates for fingernails were greater than 90% 6 months after completion of 2 treatment cycles. Clinical and mycologic cure rates for toenails were 84 and 98%, respectively, 9 months after completion of 3 cycles. Treatment was well tolerated; adverse events (mostly mild) occurred in 4.6% of patients. CONCLUSION: A 1-week intermittent itraconazole dosing regimen is a safe and effective treatment for onychomycosis.     

Amorolfine and itraconazole combination for severe toenail onychomycosis; results of an open randomized trial in Spain

Objective In an open, randomized, clinical study of toenail onychomycosis with matrix area involvement, two alternative regimens of topical amorolfine/oral itraconazole therapy were compared with itraconazole monotherapy.
Patients/Methods A total of 131 patients were randomized to treatment. Patients in the combination groups were treated with amorolfine 5% nail lacquer (Loceryl®, Galderma Laboratories) once weekly for 24 weeks and 200 mg itraconazole once daily for 6 weeks (Group AI-6) or 12 weeks (Group AI-12). A control group received itraconazole monotherapy for 12 weeks (Group I-12). Strict inclusion criteria specified that subjects had to have onychomycosis of the toenails with matrix area involvement and/or > 80% total nail surface involvement. Mycological evaluations using both microscopic examination and culture of nail samples were performed at weeks 12 and 24. A stringent assessment of outcome at study end combined the results of mycological and clinical outcomes into a global cure rate. Safety was also assessed.
Results At week 12, mycological cure was attained in 42 of 45 patients (93·3%) in group AI-6, 29 of 35 patients (82·9%) in group AI-12, and 14 of 34 patients in group I-12. The difference between both combination groups and the control group were significant ( P  < 0·001). The global cure rate at week 24 was 83·7% (36 patients) in group AI-6, 93·9% (31 patients) in group AI-12, and 68·8% (22 patients) in group I-12. The difference between the AI-12 group and itraconazole monotherapy was significant ( P  < 0·05).
Conclusions These results indicate that amorolfine combination therapy represents an improved treatment strategy for patients with severe onychomycosis.