伊曲康唑治疗血液病患者侵袭性真菌感染的多中心回顾性分析

目的 观察伊曲康唑在治疗血液病及造血干细胞移植(HSCT)后患者侵袭性真菌感染(IFI)的疗效和安全性.方法 采取开放、多中心回顾性研究的方法 ,选择2007年1-7月确诊、临床诊断和拟诊IFI的血液病或HSCT患者666例,给予静脉伊曲康唑,按前2天200ms/次、12h静脉滴注1次,第3天起200 ms/次,每天静脉滴注1次的方案治疗,并根据病情序贯伊曲康哗口服液或胶囊.根据临床和微生物学疗效标准,综合评价该药物的疗效,并观察其安全性.结果 全部患者抗真菌治疗的退热有效率为70.1%,治疗有效率为69.5%,其中确诊、临床诊断和拟诊IFI患者的有效率分别为73.7%、68.1%、68.2%,其问差异无统计学意义(P=0.380).全部患者中有58例(8.7%)出现与伊曲康唑相关的不良事件,主要表现为轻中度的肝胆系统和胃肠系统功能受损.结论 伊曲康唑是治疗血液病及HSCT患者IFI有效且安全的药物,适用于抗真菌的经验治疗.     

伊曲康唑促进结肠癌细胞自噬的作用及机制研究

目的 研究伊曲康唑促进人结肠癌细胞SW480自噬的作用及机制.方法 通过MTT法及克隆形成实验检测伊曲康唑对细胞生长增殖的影响,采用免疫荧光及免疫印迹检测伊曲康唑对自噬相关标志蛋白的表达,免疫印迹检测AKT-mTOR信号通路关键蛋白的表达.结果 伊曲康唑显著抑制SW480细胞的增殖速率,并且抑制程度呈药物浓度依赖性.免疫荧光和免疫印迹实验结果表明,伊曲康唑促进细胞自噬,并通过调控AKT-mTOR信号通路来实现.结论 伊曲康挫通过抑制AKT-mTOR信号通路来促进结肠癌细胞自噬.     

伊曲康唑治疗真菌性角膜炎的临床效果研究

目的研究伊曲康唑治疗真菌性角膜炎临床效果,为合理用药提供参考依据。方法选择2011年3月-2014年2月收治的36例真菌性角膜炎患者为观察组,采用伊曲康唑+两性霉素B+氟康唑滴眼液治疗,回顾性调查2005年3月-2011年3月收治的36例真菌性角膜炎患者临床资料为对照组,给予两性霉素B+氟康唑滴眼液治疗,连续治疗1个月后对两组治疗效果进行评估并记录。结果治疗有效率观察组为97.2%、对照组为88.9%,治疗有效率观察组高于对照组,差异有统计学意义(P<0.05);观察组患者的角膜溃疡、前房积脓、畏光流泪恢复时间均明显短于对照组,差异有统计学意义(P<0.05);两组患者在治疗过程中均无明显不良反应发生。结论在两性霉素B和氟康唑的基础上加用伊曲康唑治疗真菌性角膜炎效果,优于仅应用两性霉素B和氟康唑,且可缩短治疗所需时间,治疗安全性较好,值得临床推广。     

Comparison of the therapeutic efficacy of oral doses of fluconazole and itraconazole in a guinea pig model of dermatophytosis

The therapeutic efficacy of orally administered fluconazole (FLCZ) and itraconazole (ITCZ) in a guinea pig model of dermatophytosis was compared, using the infection intensity of local skin tissue as an index. After Trichophyton mentagrophytes infections had been established in the test animals, the antifungal agents were administered once per day for 14 days. FLCZ had a dose-dependent therapeutic effect and significantly ameliorated infections at doses of 10 and 20 mg/kg per day (both P < 0.01) compared with the untreated control group. The pathogen could not be cultured from previously infected skin tissue from 11% of the animals treated with FLCZ at 10 mg/kg per day, and from 20% of the animals treated with FLCZ at 20 mg/kg per day. The therapeutic efficacy of FLCZ was approximately equal to that of ITCZ administered at the same doses. These results suggest that FLCZ may be a useful treatment for dermatophytosis. Received: August 9, 1999 / Accepted: November 26, 1999     

恶性血液病合并侵袭性真菌感染76例临床观察

  目的 探讨恶性血液病合并侵袭性真菌感染（IFI）的易感因素、临床特点、疗效和不良反应。方法 回顾性分析76例恶性血液病合并IFI患者的易感因素、临床特点,比较伊曲康唑与两性霉素B的疗效及安全性。结果 76例恶性血液病合并IFI患者应用广谱抗生素者68例（89.5%）,化疗2个疗程以上者64例（84.2%）,中性粒细胞缺乏者43例（56.6%）,长期应用糖皮质激素者34例（44.7%）,中心或外周静脉置管者27例（35.5%）。伊曲康唑和两性霉素B治疗恶性血液病合并IFI的总有效率为60.5%和61.5%（P=0.929）;两组间不良反应对比只在低钾血症方面有差异（14.0%比42.4%,P=0.005）。结论 化疗、应用广谱抗生素、中性粒细胞缺乏等是恶性血液病合并IFI的易感因素。伊曲康唑治疗恶性血液病IFI疗效与两性霉素B相当,但不良反应较少且轻微。     

In Vitro Evaluation of Cytochrome P450-mediated Drug Interactions between Cytarabine,Idarubicin, Itraconazole and Caspofungin

Purpose: Antifungal prophylaxis is an important component of induction therapy for patients with acute myeloid leukemia (AML). Azole antifungal agents are increasingly used in this context. In vitro assays were performed to assess whether cytochrome P450 (CYP450) enzymes were affected by combinations of cytarabine or idarubicin with itraconazole or caspofungin.

Methods: The high throughput microtiter assay was used to determine whether cytarabine, idarubicin and itraconazole or caspofungin were CYP450 isoenzyme substrates, inhibitors of CYP450 isoenzymes, and to determine potential CYP450 metabolism interactions between these agents.

Results: Idarubicin is a substrate for CYP450 2D6 and 2C9. Cytarabine is a substrate of CYP450 3A4. Idarubicin inhibits CYP450 2D6, and cytarabine, itraconazole, and caspofungin inhibit CYP450 3A4. Cytarabine metabolism was significantly decreased when combined with caspofungin or itraconazole.

Conclusions: The inhibition of cytarabine metabolism may have important clinical implications. These in vitro findings warrant investigation with in vivo pharmacokinetic studies.     

伊曲康唑和γ-干扰素对裸小鼠、昆明种小鼠外周血IFN-γ、IL-10的影响

目的研究伊曲康唑和γ-干扰素治疗分别感染白念珠菌和新生隐球菌裸小鼠、昆明种小鼠外周血细胞因子IFN-γ、IL-10的改变及其临床意义。方法将白念珠菌和新生隐球菌分别注射入裸小鼠、昆明种小鼠体内,诱导成动物模型。用ELISA法检测IFN-γ和IL-10的水平。结果经过伊曲康唑和γ-干扰素治疗后,其外周血的IFN—γ上升而IL-10下降。结论伊曲康唑和γ-干扰素对真菌感染小鼠免疫功能的调节起着重要作用。     

Formulation of parenteral microemulsion containing itraconazole

The aim of this study was to develop an aqueous parenteral formulation containing itraconazole (ITZ) using an o/w microemulsion system. A mixture of benzyl alcohol and medium chain triglyceride (3/1) was chosen as the oil phase. Pseudoternary phase diagrams of the microemulsion formations were constructed in order to determine the optimum ratio of oils, the concentration range of surfactant and cosurfactant and the optimum ratio between them. Consequently, the suitability of the chosen microemulsion system as a parenteral formulation was evaluated using droplet size analysis and hemolysis tests. Among the surfactants and cosurfactants screened, a mixture of polyoxyethylene (50) hydrogenated castor oil and ethanol (3/1) showed the largest o/w microemulsion region in the phase diagram. The average droplet size of the microemulsions was < 150 nm, and the hemolysis test showed this formulation to be nontoxic to red blood cells. The pharmacokinetic profiles of the ITZ-microemulsion for itraconazole and its major metabolite, hydroxyitraconazole, were compared with those of a PEG 400 solution and cyclodextrin formulations in rats. Overall, these results highlight the potential of an ITZ-microemulsion formulation for the parenteral route.     

HPLC-荧光法测定兔血浆中伊曲康唑及其代谢产物羟基伊曲康唑的浓度

目的:建立可同时测定兔血浆中伊曲康唑(ITZ)及其代谢产物羟基伊曲康唑(HITZ)浓度的高效液相色谱-荧光法。方法:色谱柱为Agilent Eclipse C18,流动相为0.1%三乙胺缓冲液(85%磷酸调pH为2.5)-乙腈(63∶37),流速为1.0mL.min-1,荧光检测激发波长为260nm,发射波长为365nm,柱温为室温。结果:ITZ和HITZ的线性范围分别为7.4~2 960(r=0.999 1)、5.4~2 160ng.mL-1(r=0.999 3),检测限分别为0.518、0.318ng.mL-1;ITZ、HITZ的提取回收率和方法回收率均在80%以上,日内、日间RSD均小于4.47%。结论:所建立的检测方法操作简便、灵敏度高、专一性强、结果可靠,可用于兔血浆中ITZ和HITZ浓度的同时测定和药动学研究。     

伊曲康唑自乳化液的制备及质量评价

目的:制备伊曲康唑自乳化液并对其进行质量评价。方法:通过溶解度试验,油相与各种乳化剂、助乳化剂的配伍选择筛选自乳化液的处方。考察该乳化液经水稀释后形成微乳的形态、粒径和Zeta电位,并测定载药量。结果:该自乳化液处方为油相维生素E醋酸酯,乳化剂TranscutolP,助乳化剂CremophorRH40,三者比例为3:12:5。微乳在透射电镜下呈球形,分布均匀,粒径为(296.1±90.7)nm,Zeta电位为(—13.2±1.6)mV,载药量为9.88%。结论:所制自乳化液质量稳定可靠。