Cutaneous distribution of orally administered itraconazole in guinea pigs, studied by autoradiography

Background Itraconazole is an orally active antifungal lipophilic drug with high affinity for sebum and keratinocytes. Aim The aim of the study was to investigate the routes of percutaneous egression and the sites of cutaneous action/storage of ³H-labelled itraconazole in an experimental animal model. Material and methods Hartley guinea pigs were dosed orally by gavage for 2 consecutive days at 10 mg/kg/day ³H-itraconazole dissolved in polyethylene glycol 200. At various time points after the second gavage, small full-thickness samples of dorsal skin were excised and processed using dry-apposing autoradiography. Results Our research revealed an accumulation of silver grains over the epidermis and its appendages (hair follicle and sebaceous gland), the dermal fat tissue and the hypodermal muscle tissue on tissue sections at 6, 24 and 48 h time intervals, whereas at the remaining time points (96, 168 and 336 h) the silver grain density was markedly decreased to background level. Discussion The present histological distribution data support the current method of oral treatment with itraconazole as the treatment schedule of choice to eradicate infective organisms residing in the deeper skin layers.     

伊曲康唑不良反应的国内文献综述

目的：了解伊曲康唑的不良反应及安全性。资料与方法：手工检索《中华皮肤科杂志》等3种中文专业期刊，从对照试验的文献中提取治疗例数和各种不良反应例数，计算发生率。结果：共有14725例涉及有关安全性的报道。伊曲康唑不良反应总的发生率约为1．57％。结论：伊曲康唑较为安全。     

Influence of an acidic beverage (Coca-Cola) on the absorption of itraconazole

Objective: To evaluate the effectiveness of Coca-Cola in enhancing the absorption of itraconazole. Methods: Eight healthy volunteers were randomized to receive two treatment sequences in a two-way crossover design with a 1-week wash-out period separating each study treatment. Treatment I, the control, consisted of 100 mg itraconazole with 325 ml water. Treatment II was identical to treatment I, except that itraconazole was administered with 325 ml of Coca-Cola (pH 2.5). Results: Serum itraconazole concentrations, after administration with Coca-Cola (treatment II), were higher than after administration with water (treatment I). The mean AUC was 1.12 vs 2.02 μg · h · ml⁻¹, the mean C_max was 0.14 vs 0.31 μg · ml⁻¹and the mean t_max was 2.56 vs 3.38 h in treatments I and II, respectively. Conclusion: The absorption of itraconazole can be enhanced by Coca-Cola. Received: 4 November 1996 / Accepted in revised form: 21 January 1997     

Disseminated histoplasmosis in a non-immunocompromised host

Histoplasma infections in Europe are rare, and acute disseminated histoplasmosis has only been observed in immunocompromised persons. We describe a case of acute disseminated histoplasmosis in a young, nonimmunocompromised European woman. The probable source of infection was Sri Lanka or the Maldives. At presentation she was severely ill with fever, lymphadenopathy, anemia, thrombocytopenia, hepatosplenomegaly, and polyserositis. Histologically, myelofibrosis and osteosclerosis were observed with extramedullary hematopoiesis. Histoplasma capsulatum yeasts were detected in bone marrow trephine biopsy by methenamine silver staining. Treatment with conventional and liposomal amphotericin B and subsequent itraconazole led to rapid and complete recovery.Abbreviations He Histoplasma capsulatum - AIDS acquired immunodeficiency syndrome - HIV human immunodeficiency virus     

紫外分光光度法测定伊曲康唑注射液的含量

目的建立紫外分光光度法测定伊曲康唑注射液含量的测定方法。方法采用紫外分光光度法测定伊曲康唑注射液的含量,测定波长为262nm。结果线性范围0~38.08μg·ml-1,伊曲康唑的平均回收率为99.1%,RSD为0.24%,r=0.9999(n=6)。结论该法方便快速准确,可作为伊曲康唑注射液含量测定的方法。     

The Antifungal Itraconazole Is a Potent Inhibitor of Chikungunya Virus Replication

Chikungunya virus (CHIKV) is the causative agent of chikungunya fever, a disabling disease that can cause long-term severe arthritis. Since the last large CHIKV outbreak in 2015, the reemergence of the virus represents a serious public health concern. The morbidity associated with viral infection emphasizes the need for the development of specific anti-CHIKV drugs. Herein, we describe the development and characterization of a CHIKV reporter replicon cell line and its use in replicon-based screenings. We tested 960 compounds from MMV/DNDi Open Box libraries and identified four candidates with interesting antiviral activities, which were confirmed in viral infection assays employing CHIKV-nanoluc and BHK-21 cells. The most noteworthy compound identified was itraconazole (ITZ), an orally available, safe, and cheap antifungal, that showed high selectivity indexes of >312 and >294 in both replicon-based and viral infection assays, respectively. The antiviral activity of this molecule has been described against positive-sense single stranded RNA viruses (+ssRNA) and was related to cholesterol metabolism that could affect the formation of the replication organelles. Although its precise mechanism of action against CHIKV still needs to be elucidated, our results demonstrate that ITZ is a potent inhibitor of the viral replication that could be repurposed as a broad-spectrum antiviral.     

伊曲康唑注射液制备研究

介绍了伊曲康唑注射液的制备和质量控制,对制得的伊曲康唑注射液的含量和稳定性等作了研究,结果证明制备方法良好,样品质量可控。     

伊曲康唑不同治疗方案对比特比萘芬治疗甲真菌病疗效和安全性的Meta分析

目的:系统评价伊曲康唑不同治疗方案对比特比萘芬治疗甲真菌病的临床疗效与安全性,以为临床治疗提供循证参考。方法:计算机检索Pub Med、EMBase、Medline、The Cochrane Library、中国期刊全文数据库、维普中文科技期刊全文数据库、万方数字化期刊全文库,收集伊曲康唑对比特比萘芬治疗甲真菌病的随机对照试验(RCT),提取资料并评价质量后,采用Rev Man 5.2统计软件进行Meta分析。结果:共纳入11项RCT,合计1 886例患者。Meta分析结果显示,伊曲康唑连续治疗的临床治愈率[RR=0.94,95%CI(0.76,1.18),P=0.61]与特比萘芬比较差异无统计学意义,而真菌学治愈率[RR=0.80,95%CI(0.68,0.95),P=0.01]和总治愈率低于特比萘芬,两组比较差异有统计学意义;伊曲康唑冲击治疗的临床治愈率[RR=0.75,95%CI(0.65,0.87),P<0.000]和总治愈率[OR=0.39,95%CI(0.27,0.55),P<0.000]低于特比萘芬,而真菌学治愈率与特比萘芬比较差异无统计学意义[RR=0.82,95%CI(0.63,1.07),P=0.14];两组患者消化系统不良反应发生率比较,差异无统计学意义[OR=1.02,95%CI(0.83,1.25),P=0.86]。结论:伊曲康唑不同治疗方案治疗甲真菌病的疗效均低于特比萘芬,安全性相似。由于纳入研究数量较少、质量一般,该结论尚有待大样本、高质量的RCT进一步验证。     

变应性支气管肺曲菌病1例并文献复习

目的:提高对变应性支气管肺曲菌病(ABPA)的认识并引起对该病的重视.方法:对1例ABPA患者临床资料进行分析,并结合文献进行复习.结果:ABPA是一种慢性、免疫介导的,对寄生繁殖的曲菌过敏导致的非感染性、炎症性肺部疾病,常发生在支气管哮喘的患者.结论:目前对该病的诊断应采取多种手段,包括纤支镜检查,痰培养及影像学、免疫学等;长期吸入糖皮质激素与口服伊曲康唑能达到较好治疗效果,且最大限度减少副作用.     

伊曲康唑醇质体的制备及体外经皮渗透研究

目的考察醇质体凝胶作为伊曲康唑透皮给药载体的可行性。方法采用注入法制备伊曲康唑醇质体进而用卡波姆制备成凝胶,采用透皮扩散试验仪对大鼠皮肤进行体外经皮渗透实验;以HPLC测定药物含量求算积累渗透量及稳态透皮速率,并测定药物在皮肤表皮和真皮中的滞留量。结果伊曲康唑醇质体凝胶的经皮渗透率是其水溶液的9.20倍,是体积分数为30%乙醇环糊精溶液的1.97倍。结论醇质体凝胶能提高伊曲康唑的透皮速率,增加药物在皮肤内的滞留量。