伊曲康唑影响的药代动力学相互作用研究进展

伊曲康唑为三唑类广谱抗真菌药,临床应用广泛,具有CYP3A4和P-糖蛋白抑制作用。由于临床CYP3A4和P-糖蛋白底物广泛,它们在口服药物吸收的主要部位胃肠道均有高表达,同时两者的底物具有显著的重叠性,由此导致的受伊曲康唑影响的药代动力学相互作用广泛产生,甚至引起显著的临床意义。本文综述并讨论了受其影响的药代动力学相互作用研究,以促进临床的安全用药。     

Risks Involved in Selective Decontamination in Immunocompromised Patients.

Summary: Selective oral and systemic decontamination are widely discussed when it comes to the prophylaxis of bacterial and fungal infections in immunocompromised patients. The number of such patients is clearly rising due to the aggressiveness of modern medicine. Host defence is based on a variety of factors including the barrier function of mucosal surfaces as well as the phagocytic system provided by the blood. It seems helpful to distinguish between three different stages of immunodeficiency: "Minor immunodeficiency", "immunodeficiency" (in a stricter sense), "major immunodeficiency". When it comes to the choice of measures to be taken to protect the host, it is not only needed to consider the microbes already present but also the present state of defence mechanisms. When invasive fungal infections in particular have to be prevented, several drugs have to be discussed, As conventional antifun-gals have not met all expectations there is clear need for new drugs such as itraconazole.     

伊曲康唑抑制小鼠树突状细胞迁移及MMP-2、MMP-3、MMP-12与RANTES的分泌

目的：明确伊曲康唑对小鼠骨髓来源树突状细胞（DCs）迁移功能及基质金属蛋白酶(MMP)-2、MMP-3、MMP-12与趋化因子RANTES分泌的影响。方法：取小鼠骨髓单核细胞,重组小鼠粒—巨噬细胞集落刺激因子(rmGM-CSF)诱导至第8天,将DCs分为对照组、伊曲康唑处理组（0.25、0.5、1 μM）,细胞计数试剂盒（CCK-8）和Transwell分别检测不同浓度伊曲康唑对DCs活性及DCs迁移情况;Luminex液相芯片技术检测MMP-2、MMP-3、MMP-8、 MMP-12、CCL5/RANTES的分泌;流式细胞仪检测MHCII、CD80、CD86及CCR7的表达。结果：伊曲康唑对树突状细胞毒性呈时间及剂量依赖;伊曲康唑组细胞迁移率低于对照组,差异有统计学意义（P<0.05）。伊曲康唑组MMP-2、MMP-3、MMP-12和RANTES水平均低于对照组,差异均有统计学意义（均P<0.05）。伊曲康唑组和对照组中CCR7和MMP-8水平比较,差异均无统计学意义（P>0.05）。结论：伊曲康可唑抑制树突状细胞的迁移及相关MMPs和RANTES的表达。     

两性霉素B和伊曲康唑的体外联合药敏试验分析

目的 研究两性霉素B和伊曲康唑在酵母菌体外联合药敏试验中的相互作用,为临床用药提供参考依据.方法 参照美国国家临床试验标准化委员会(NCCLS)提出的标准(M27-A方案),采用棋盘微量稀释法对28株酵母菌(隐球菌和念珠菌)进行了二性霉素B和伊曲康唑的体外联合药敏试验.结果 发现联合用药时各药物的MIC几何均值比单用有...     

Effect of the vehicle on the topical itraconazole efficacy for treating corneal ulcers caused by Aspergillus fumigatus

Background:  The clinical behaviour of mycotic keratitis is aggressive, and the options for treating it are limited. This poses a need to explore new options for efficacious, low-cost treatment. Recent evidence suggests that topical itraconazole may be useful for treating this entity and that it may be possible to improve its efficacy using a suitable vehicle.
Methods:  We included 12 New Zealand white (NZW) rabbits (24 eyes). The rabbits were infected with pathogenic strains of Aspergillus fumigatus and subsequently randomized to receive every 2 h for 5 weeks two different preparations of topical itraconazole 1%. In group 1 (12 eyes), ricinus oil and in group 2 (12 eyes), Systane were used as vehicle. Rabbits were evaluated every week by a masked ophthalmologist to determine the treatment response.
Results:  The size of the ulcers was similar in the two groups at the baseline: group 1: 12.7 ± 2.7 mm (median 12.8, range 9.8–15.5 mm); and group 2: 12.3 ± 3.1 mm (median 12.1, range 9.8–20.8; P  = 0.67). Although both groups responded well to the treatment, the response was better in the group 2, especially in weeks 2 and 3: week 1: 12.7 ± 2.7 vs. 9.3 ± 4.61 mm ( P  = 0.1); week 2: 9.4 ± 3.4 vs. 4.1 ± 2.9 mm ( P  = 0.004); week 3: 5.0 ± 3.4 vs. 1.7 ± 1.0 mm ( P  = 0.004); week 4: 1.9 ± 1.9 vs. 1.0 ± 1.2 mm ( P  = 0.1); and week 5: 0.68 ± 1.2 vs. 0.0 ± 0.0 mm ( P  = 0.3).
Conclusion:  Topical itraconazole may be useful for treating corneal ulcers caused by Aspergillus fumigatus , and its efficacy seems to be related with the vehicle solubility.     

Effect of itraconazole on the cornea in a murine suture model and penetrating keratoplasty model

AIM: To investigate the anti-(lymph)angiogenic and/or anti-inflammatory effect of itraconazole in a corneal suture model and penetrating keratoplasty (PK) model. METHODS: Graft survival, corneal neovascularization, and corneal lymphangiogenesis were compared among itraconazole, amphotericin B, dexamethasone, phosphate buffered saline (PBS) and surgery-only groups following subconjunctival injection in mice that underwent PK and corneal suture. Immunohistochemical staining and analysis were performed in each group. Real-time polymerase chain reaction (RT-PCR) was performed to quantify the expression of inflammatory cytokines (TNF-alpha, IL-6) and vascular endothelial growth factor (VEGF)-A, VEGF-C, VEGFR-2, and VEGFR-3. RESULTS: In the suture model, the itraconazole group showed less angiogenesis, less lymphangiogenesis, and less inflammatory infiltration than the PBS group (all P<0.05). The itraconazole group showed reduced expression of VEGF-A, VEGFR-2, TNF-alpha, IL-6 than the PBS group (all P<0.05). In PK model, the two-month graft survival rate was 28.57% in itraconazole group, 62.50% in dexamethasone group, 12.50% in PBS group, 0 in amphotericin B group and 0 in surgery-only group. Graft survival in the itraconazole group was higher than that in the amphotericin, PBS and surgery-only group (P=0.057, 0.096, 0.012, respectively). The itraconazole group showed less total angiogenesis and lymphangiogenesis than PBS group (all P<0.05). CONCLUSION: Itraconazole decrease neovascularization, lymphangiogenesis, and inflammation in both a corneal suture model and PK model. Itraconazole has anti-(lymph)-angiogenic and anti-inflammatory effects in addition to its intrinsic antifungal effect and is therefore an alternative treatment option in cases where steroids cannot be used.     

Comparison of the Efficacy and Tolerability of Amoxycillin/Clavulanic Acid 875mg b.i.d. with Cefuroxime 500mg b.i.d. in the Treatment of Chronic and Acute Exacerbation of Chronic Sinusitis in Adults

Abstract

The efficacy and safety of amoxycillin/clavulanic acid (AMX/CA) (875/125mg b.i.d. for 14 days) were compared with that of cefuroxime axetil (500mg b.i.d. for 14 days) in a multicenter, open, parallel-group, randomized clinical trial in 206 adults with chronic or acute exacerbation of chronic sinusitis. Clinical response was similar, with 95% of AMX/CA-, and 88% of cefuroxime-treated, clinically evaluable patients cured (95% confidence interval; -0.6% to +15%). In bacteriologically evaluable patients, cure rates, defined as eradication of the original pathogen with or without re-colonization with non-pathogenic flora, were also similar, with 65% of AMX/CA- and 68% of cefuroximetreated patients cured (95% confidence interval; ?18% to +15%). However, clinical relapse was significantly higher in the cefuroxime group: 7% (7/89) of clinically evaluable patients, compared with 0% (0/98) in the AMX/CA (p=0.0049) group. A similar incidence of possible or definite adverse events related to the study drug was reported for both treatments (AMX/CA 4.4%, cefuroxime 4.3%), the most frequent being diarrhea. Four adverse events were recorded as serious or life-threatening with only one considered related to the study drug (urticaria, cefuroxime). AMX/CA 875/125mg b.i.d. for 14 days is as effective and well tolerated as cefuroxime axetil 500mg b.i.d. for 14 days in the treatment of chronic, or acute exacerbation of chronic sinusitis, but is associated with a significantly lower clinical relapse rate.