Everolimus: an update on the mechanism of action, pharmacokinetics and recent clinical trials

Abstract

Background: A growing body of evidence suggests that everolimus might offer effective immunosuppressive activity together with antiproliferative effects that may address some of the unmet needs in the long-term therapeutic management of the post-transplant patient. Objective: To summarize the emerging evidence for employing everolimus-based immunosuppression. Methods: A systematic review was conducted of the Medline, Embase and Renal Health Library (Cochrane Collaboration) databases, and of the summary publications from international transplant meetings and congresses during 2000 – 2008. Results: This article summarizes this analysis, with special focus on the pharmacokinetic characteristics of everolimus and on the results of its use in renal transplantation. Some data has also been included about the efficacy of the drug in other solid organ transplantation and in tumours. Conclusions: Everolimus is an immunosuppressant drug with proven efficacy in transplantation. When used in combination with cyclosporin, better results are obtained in renal function with low cyclosporin doses. Adverse events related to this drug are frequent and lead to moderate dropout rates.

Keywords::

• everolimus
• immunosuppressive drugs
• mTOR inhibitors
• proliferation signal inhibitors
• RAD
• renal transplantation