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伏立康唑及其在血液恶性肿瘤患者中预防系统性真菌感染的临床潜力:观点综述。

Voriconazole and its clinical potential in the prophylaxis of systemic fungal infection in patients with hematologic malignancies: a perspective review.

机构信息

Hematology Department, Complejo Hospitalario de Navarra, Pamplona, Spain, and Biomedical Research Center (NavarraBiomed), Navarra, Spain.

出版信息

Ther Adv Hematol. 2013 Jun;4(3):217-30. doi: 10.1177/2040620713481796.

DOI:10.1177/2040620713481796
PMID:23730499
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3666449/
Abstract

Invasive fungal infections (IFIs) have become high prevalence in patients with hematologic malignancies. Drug-based strategies for IFIs include various approaches such as prophylactic, empiric, preemptive, and directed treatment. Prophylaxis is an attractive strategy in high-risk patients, given the lack of reliable diagnostics and the high mortality rate associated with IFIs. Prophylaxis includes the use of antifungal drugs in all patients at risk. An ideal antifungal compound for prophylaxis should have a potent and broad activity, be available both orally and intravenously, and have a low toxicity profile. Voriconazole fulfills all these criteria. The clinical efficacy of voriconazole against the majority of fungal pathogens makes it potentially very useful for the prevention of IFIs in patients with hematologic malignancies. Voriconazole appears to be very effective for the primary and secondary prevention of IFIs in these patients and recipients of allogeneic hematopoietic stem-cell transplantation. Randomized controlled trials evaluating voriconazole as primary antifungal prophylaxis in patients with neutropenia treated for a variety of hematologic malignancies have been performed, confirming its value as a prophylactic agent. Voriconazole is generally safe and well tolerated; however, its use is also associated with a number of concerns. In most patients with hematologic malignancies there is the potential for pharmacokinetic drug-drug interactions given that voriconazole is metabolized through the P450 cytochrome system.

摘要

侵袭性真菌感染(IFI)在血液恶性肿瘤患者中已变得高发。IFI 的药物治疗策略包括各种方法,如预防、经验性、先发制人和靶向治疗。鉴于缺乏可靠的诊断方法和 IFI 相关的高死亡率,预防是高危患者的一种有吸引力的策略。预防包括对所有有风险的患者使用抗真菌药物。预防用的理想抗真菌药物应该具有强大而广泛的活性,既可以口服也可以静脉注射,并且具有低毒性特征。伏立康唑符合所有这些标准。伏立康唑对大多数真菌病原体的临床疗效使其对血液恶性肿瘤患者 IFI 的预防具有潜在的重要意义。伏立康唑似乎对这些患者和异基因造血干细胞移植受者的 IFI 的原发性和继发性预防非常有效。已经进行了评估伏立康唑作为中性粒细胞减少症患者多种血液恶性肿瘤治疗的一线抗真菌预防的随机对照试验,证实了其作为预防药物的价值。伏立康唑通常安全且耐受良好;然而,其使用也存在一些问题。由于伏立康唑通过细胞色素 P450 系统代谢,大多数血液恶性肿瘤患者存在药物-药物相互作用的药代动力学潜力。

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本文引用的文献

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A hematology consensus agreement on antifungal strategies for neutropenic patients with hematological malignancies and stem cell transplant recipients. Gruppo Italiano Malattie Ematologiche dell'Adulto, Gruppo Italiano Trapianto di Midollo Osseo, Associazione Italiana Ematologia ed Oncologia Pediatrica, Invasive Fungal Infections Cooperative Group of the European Organization for Research and Treatment of Cancer and Sorveglianza Epidemiologica delle Infezioni Fungine nelle Emopatie Maligne.血液病成人意大利研究组、骨髓移植意大利研究组、意大利儿科血液学和肿瘤学会、欧洲癌症研究与治疗组织侵袭性真菌感染合作组和恶性血液病真菌感染监测研究组关于血液恶性肿瘤和造血干细胞移植受者中性粒细胞减少患者抗真菌策略的血液学共识协议。
Hematol Oncol. 2013 Sep;31(3):117-26. doi: 10.1002/hon.2031. Epub 2012 Oct 5.
2
Increased incidence of cutaneous squamous cell carcinoma in lung transplant recipients taking long-term voriconazole.长期服用伏立康唑的肺移植受者皮肤鳞状细胞癌发病率增加。
J Heart Lung Transplant. 2012 Nov;31(11):1177-81. doi: 10.1016/j.healun.2012.05.003. Epub 2012 Jul 27.
3
Challenging recommended oral and intravenous voriconazole doses for improved efficacy and safety: population pharmacokinetics-based analysis of adult patients with invasive fungal infections.挑战推荐的口服和静脉伏立康唑剂量以提高疗效和安全性:基于群体药代动力学分析成人侵袭性真菌感染患者。
Clin Infect Dis. 2012 Aug;55(3):381-90. doi: 10.1093/cid/cis437. Epub 2012 May 18.
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