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Sirolimus: Continuing the Evolution of Transplant Immunosuppression

2000; SAGE Publishing; Volume: 34; Issue: 9 Linguagem: Inglês

10.1345/aph.19380

1542-6270

Gordon R. Ingle, Theodore M. Sievers, Curtis Holt,

Adenosine and Purinergic Signaling

OBJECTIVE: To review the pharmacology, pharmacokinetics, clinical efficacy, adverse effects, and economic issues associated with sirolimus, the most recent immunosuppressive agent approved for kidney transplantation. DATA SOURCES: A MEDLINE search (1966–June 2000) was completed to identify primary and review articles. In addition, abstracts from recent meetings on transplantation were reviewed for information and research on sirolimus. STUDY SELECTION AND DATA EXTRACTION: Blinded, randomized, controlled studies were the goal, but, as with most newly approved immunosuppressive agents, a significant amount of information on sirolimus is not available in this optimal form. All articles were assessed and all pertinent information was incorporated in this review. DATA SYNTHESIS: Sirolimus is structurally related to the immunosuppressive agent tacrolimus, and retains a pharmacokinetic and drug interaction profile similar to that of the calcineurin inhibitors, cyclosporine and tacrolimus. However, the novel mechanism of action of sirolimus differs significantly from these agents, as does its adverse effect profile. The most significant adverse reaction is hyperlipidemia. Clinical experience with sirolimus has allowed transplant centers to expand its use into other areas of transplantation as well as certain autoimmune disorders. CONCLUSIONS: The definitive role of sirolimus will continue to be determined; however, sirolimus offers an excellent addition to the transplant immunosuppression armamentarium.