Long-term outcome of everolimus treatment in transplant patients

IF 0.1 Q4 TRANSPLANTATION Transplant Research and Risk Management Pub Date : 2011-05-13 DOI:10.2147/TRRM.S12212
M. Salvadori, E. Bertoni
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引用次数: 11

Abstract

Correspondence: Maurizio Salvadori Renal Unit, Careggi University Hospital, viale Pieraccini 18, 50139 Florence, italy Tel +39 055 794 9269 Fax +39 055 435 878 email maurizio.salvadori@unifi.it Abstract: The authors review the use of everolimus in long-term studies both in renal and heart transplantation. The pharmacokinetic and pharmacodynamic differences between everolimus and its parent drug, sirolimus are discussed. The improved pharmacokinetic, in particular the improved bioavailability, the reduced half-time and the reduced binding to plasma protein makes everolimus the first choice among the proliferation signal inhibitors. Everolimus is given in almost all studies in association with cyclosporine, but fixed doses of this drug can cause nephrotoxicity. The first studies used everolimus and CsA in fixed doses, but later studies with reduced CsA doses revealed which revealed improved outcomes. Finally, therapeutic drug monitoring became the better choice for both drugs. Recently very high everolimus exposure allowed the use of very low CsA exposure with improvement of the worse side effects linked to the CsA standard dose. The Zeus study revealed a complete and safe CsA withdrawal, thanks to everolimus and mycophenolic acid. In heart transplantation, everolimus resulted in improved outcomes with respect to antiproliferative drugs such as mycophenolic acid and azathioprine. Along with antirejection properties, everolimus provided evidence for antiproliferative effects on several cells. This resulted in fewer viral infections (mainly CMV), anti-atherosclerotic properties (mainly important in heart transplantation, and antineoplastic effect. The latter activity resulted in lower cancer incidence in transplant patients treated by everolimus. An important piece of evidence for this activity is documented by the use of everolimus in the treatment of some cancers, including renal cancer, neuroendocrine cancers and hepatocellular cancers, also outside the field of transplantation.
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依维莫司治疗移植患者的长期疗效
通信:Maurizio Salvadori肾科,Careggi大学医院,viale Pieraccini 18, 50139佛罗伦萨,意大利电话+39 055 794 9269传真+39 055 435 878电子邮件maurizio.salvadori@unifi.it摘要:作者回顾了依维莫司在肾脏和心脏移植的长期研究中的使用。讨论了依维莫司与其母体药物西罗莫司的药代动力学和药效学差异。改善的药代动力学,特别是提高的生物利用度,缩短的半衰期和减少与血浆蛋白的结合使依维莫司成为增殖信号抑制剂的首选。在几乎所有与环孢素相关的研究中,都给予依维莫司,但这种药物的固定剂量可引起肾毒性。最初的研究使用固定剂量的依维莫司和CsA,但后来的研究表明减少CsA的剂量可以改善结果。最后,治疗药物监测成为两种药物更好的选择。最近,非常高的依维莫司暴露量使得使用非常低的CsA暴露量可以改善与CsA标准剂量相关的更严重的副作用。Zeus研究显示,由于依维莫司和霉酚酸,CsA完全安全停用。在心脏移植中,依维莫司与抗增殖药物如霉酚酸和硫唑嘌呤相比可改善预后。依维莫司除具有抗排斥作用外,还对多种细胞具有抗增殖作用。这导致较少的病毒感染(主要是巨细胞病毒),抗动脉粥样硬化特性(主要在心脏移植中重要)和抗肿瘤作用。后一种活性导致接受依维莫司治疗的移植患者癌症发病率降低。这种活性的一个重要证据是,依维莫司用于治疗一些癌症,包括肾癌、神经内分泌癌和肝细胞癌,这些癌症也不属于移植领域。
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来源期刊
CiteScore
0.70
自引率
0.00%
发文量
6
审稿时长
16 weeks
期刊最新文献
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