Macrolides Everolimus

Sirolimus is currently the only FDA-approved ToR inhibitor. One of its derivatives, everolimus, is in phase III clinical trials and has been approved for use in some European countries.30 Sirolimus is a macrolide antibiotic that has no effect on cal-cineurin phosphatase.11,31,32 Sirolimus inhibits T cell activation and proliferation by binding to and inhibiting the activation of the mammalian ToR, which suppresses cellular response to IL-2 and other cytokines (i.e., IL-4 and IL-15J.11,31 Studies have shown that sirolimus may be used safely and effectively with either cyclosporine or tacrolimus as a replacement for either azathioprine or mycophenolate mofetil.33 However, when using both sirolimus and cyclosporine as part of a patient s immunosuppressant therapy, because of a drug interaction between the two resulting in a marked increase in sirolimus concentrations, it is recommended to separate the sirolimus and cyclosporine doses by at least 4 hours. Sirolimus also can be used as an alternative agent for patients who do not tolerate calcineurin inhibitors due to nephrotoxicity or other adverse events.34... 

Everolimus (40 Afinitor ) Sirolimus (34) Macrolide antibiotic Semi-synthetic NP Microbial Anticancer Inhibits mTOR kinase activity 375-382... 

Everolimus is an immunosuppressive macrolide that also has synergistic actions with ciclosporin and interrupts the proliferative responses of vascular and bronchial smooth muscle cells. In a phase I trial, its safety profile and pharmacokinetics were assessed during a 4-week course of once-daUy sequential ascending doses (0.75, 2.5, or... 

Erythromycin increases everolimus levels. Other macrolides probably interact similarly. 

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