New Approaches to Clinical Transplantation Immunosuppression：Immunosuppressive Agents of the New Millennium

臨床移植免疫抑制的新境界：新禧年的免疫抑制劑

闕士傑(Shih-Chieh J. Chueh) ； Barry D. Kahan

《Acta Nephrologica》 14卷2期 (2000/04) Pp. 53-59

摘要

在人類堂堂邁入第三個千禧年的時代，臨床的移植專家們手中擁有了更多、更有效、更安全的免疫抑制劑。雖然“普樂可復”（tarcolimus;TRL）的出現，一度幾乎取代了以油（oil-based）為基底的“環孢靈素”（CsA）防止急性排斥的地位，但新的徵粒包含體（microemulsion）劑型環孢靈素的發明又及時彌補了二者的差異。但無論普樂可復（TRL）也好，環孢靈素（CsA）也好，他們的副作用仍然不得不讓臨床專家考慮併用其它輔助的免疫抑制劑。當（MMF）與普樂可復（TRL）或環孢靈素（CsA）併用時，雖然能降低急性排斥的比率，但同時也加重了腸胃道的不適及白血球低下的情現。而（Sirolimus; SRL）則不然，它與普樂可復（TRL）環孢靈素（CsA）併用時，雖然能降低急性排斥的比率，但同時也加重了腸胃道的不適及白血球低下的情形。而（Sirolimus; SRL）則不然，它與普樂可復（TRL）或環孢靈素（CsA）併用時，不僅能有效的降低急性排斥，同時還可以協同作用而減低普樂可復（TRL）或環孢靈素（CsA）的劑量，進一步的減少了二者的副作用。Everolimus（RAD）是比rapamycin更有親水性的類同結構物，業已問世，並展開臨床試驗測試中，雖然據聞其藥效並不如rapamycin且毒性與rapamycin相似。Basiliximub及Daclizumb，一種能與IL-2受器結合的單株抗體，因為在移植的早期能有效的保護移植腎，業已與環孢靈素（CsA）、類固醇併用於抗排斥的療法的標準療程中，且目前並無明顯的副作用。FTY720，一種更新的藥，是經由其它截然不同的機轉達到免疫抑制的目的，而且號稱不會影響到周邊的淋巴球，目前已使用在實驗及初期臨床試驗中。有效的使用免疫抑制劑及免疫協調劑，臨床醫師不僅能藉由良善的免疫抑制效來改善移植病人的癒後，還能降低病人的發病率，減少病人的不便，也能詳制醫療的耗費。

關鍵字

環孢靈素 ； 普樂可複

並列摘要

As we enter the third millennium, transplant clinicians have available an array of new immunosuppressants with distinct profiles of efficacy and safety. Although some studies have suggested the benefits of tacrolimus (TRL) over the oil-based formulation of cyclosporine (CsA) as a primary agent for prophylaxis of acute rejection, the use of the microemulsion CsA formulation has eliminated this difference. Indeed, the adverse effect profiles of both CsA and TRL remain considerable and demand the introduction of synergistic immunosuppressants. While mycophenolate mofetil (MMF) used concomitantly with either CsA or TRL has reduced acute rejection rates, it exerts only additive effects with CsA or TRL and is associated with gastrointestinal and leukopenic side effects. In contrast, rapamycin (sirolimus; SRL) exerts synergistic effects not only to lower the rate of acute rejection episodes but also to permit reduced doses of CsA or TRL. Everolimus (RAD), a rapamycin analogue with greater hydrophilicity, is currently undergoing clinical trials, although preliminary data suggest lower efficacy and equal toxicity to that of SRL. Basiliximab and daclizumab, monoclonal antibodies that bind to the α-chain of the interleukin-2 receptor (IL-2R), provide additive protection of the allografts during the early posttransplant period when added to a CsA-steroid combination without any apparent adverse effects. FTY720, a novel drug acting through a totally different mechanism, has displayed potent immunosuppressive activity in preclinical and initial clinical studies, producing a reversible decrease in peripheral lymphocyte count. Utilizing combination therapy with synergistic agents, clinicians can anticipate improved patient outcomes not only in efficacy of immunosuppression, but also in reduced comorbidity, inconvenience, and cost of the therapy.

並列關鍵字

cyclosporine ； tacrolimus ； rapamycin ； everolimus ； FTY720