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Introducing everolimus (Certican) in organ transplantation: an overview of preclinical and early clinical developments.

Abstract
Everolimus (Certican) is a novel proliferation signal inhibitor with potent immunosuppressant effects that has been shown to prevent and reverse acute rejection in preclinical models of kidney, heart, and lung transplantation. These effects have been confirmed by clinical studies in which everolimus demonstrated comparable efficacy to azathioprine and mycophenolate mofetil in heart and renal transplantation, respectively, when combined with full-dose cyclosporine (CsA; Neoral). Experimental studies have also shown that everolimus inhibits smooth muscle cell proliferation and prevents neointimal thickening and transplant arteriosclerosis. Importantly, everolimus was shown to significantly reduce both the incidence and severity of cardiac allograft vasculopathy in recipients of heart transplants, which if confirmed in long-term studies, could provide a major advantage in these patients. Use of everolimus was also associated with lower rates of cytomegalovirus infection in both indications. Studies in which everolimus was combined with reduced-exposure CsA have demonstrated significantly improved renal function when compared with full-dose regimens, with no loss of efficacy. The results of preclinical and clinical studies with everolimus thus indicate that this novel proliferation signal inhibitor will be an important addition to the armamentarium by enhancing graft survival and minimizing toxicity.
AuthorsHans-Hellmut Neumayer
JournalTransplantation (Transplantation) Vol. 79 Issue 9 Suppl Pg. S72-5 (May 15 2005) ISSN: 0041-1337 [Print] United States
PMID15880019 (Publication Type: Journal Article, Review)
Chemical References
  • Immunosuppressive Agents
  • Everolimus
  • Sirolimus
Topics
  • Animals
  • Clinical Trials as Topic
  • Drug Monitoring
  • Everolimus
  • Heart Transplantation (immunology)
  • Humans
  • Immunosuppressive Agents (therapeutic use)
  • Lung Transplantation (immunology)
  • Safety
  • Sirolimus (analogs & derivatives, therapeutic use)
  • Transplantation Immunology

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