title: Sirolimus: continuing the evolution of transplant immunosuppression.
abstract: 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.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
authors.affiliation: Dumont-UCLA Transplant Center, University of California-Los Angeles Medical Center 90095, USA. gingle@mednet.ucla.edu
authors.forename: G R
authors.initials: GR
authors.lastname: Ingle
authors.forename: T M
authors.initials: TM
authors.lastname: Sievers
authors.forename: C D
authors.initials: CD
authors.lastname: Holt
mesh_terms: D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D016572:Cyclosporine / Q000627:therapeutic use; D006084:Graft Rejection / Q000517:prevention & control; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000191:economics / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D016377:Organ Transplantation; D012189:Retrospective Studies; D020123:Sirolimus / Q000009:adverse effects / Q000191:economics / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000305:Adrenal Cortex Hormones; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D020123:Sirolimus