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西多福韦:一种胞嘧啶无环核苷膦酸类似物治疗难治性和癌前HPV相关肛门病变的临床经验及未来展望

Cidofovir: clinical experience and future perspectives on an acyclic nucleoside phosphonate analog of cytosine in the treatment of refractory and premalignant HPV-associated anal lesions.

作者信息

Coremans Georges, Snoeck Robert

机构信息

Department of Gastroenterology, University Hospital Gasthuisberg, Herestraat 49, 3000 Leuven, Belgium.

出版信息

Expert Opin Pharmacother. 2009 Jun;10(8):1343-52. doi: 10.1517/14656560902960154.

Abstract

BACKGROUND

Cidofovir, a nucleotide analog with antiviral activity against a broad range of DNA viruses including human papilloma viruses (HPV), is available off label to clinicians.

OBJECTIVE

To provide a better knowledge of pharmacology and effects when topically applied.

METHODS

After reviewing the chemistry, physiology, and animal studies, an overview of clinical studies is provided.

RESULTS/CONCLUSIONS: Cidofovir, as a result of its antiviral and antiproliferative activity and its ability to induce apoptosis, can offer a solution for the treatment of severe recurrent HPV-induced lesions. It can also be used to attempt to treat dysplastic lesions and as an adjuvant treatment. The long-lasting antiviral activity allows infrequent dosing. As a rule, cidofovir applied on the skin is well tolerated, even in long-term treatment. The dose-limiting nephrotoxicity of the drug is not a concern in patients with a glomerular filtration rate within the normal range. Cidofovir has clearly influenced the landscape of refractory and dysplastic anogenital condylomata acuminata and its use has increased over the last decade. However, further controlled clinical trials are needed to assess the role of cidofovir and its derivatives.

摘要

背景

西多福韦是一种核苷酸类似物,对包括人乳头瘤病毒(HPV)在内的多种DNA病毒具有抗病毒活性,临床医生可在药品标签外使用该药。

目的

更深入了解局部应用西多福韦的药理作用和效果。

方法

在回顾其化学性质、生理学特性及动物研究后,对临床研究进行概述。

结果/结论:西多福韦因其抗病毒、抗增殖活性及诱导细胞凋亡的能力,可为治疗严重复发性HPV引起的病变提供一种解决方案。它也可用于尝试治疗发育异常病变及作为辅助治疗。其持久的抗病毒活性允许减少给药频率。通常,即使长期治疗,皮肤应用西多福韦的耐受性也良好。对于肾小球滤过率在正常范围内的患者,该药的剂量限制性肾毒性并非问题。西多福韦显著影响了难治性和发育异常性肛门生殖器尖锐湿疣的治疗格局,且在过去十年中其使用有所增加。然而,需要进一步的对照临床试验来评估西多福韦及其衍生物的作用。

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