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10.1517/14740338.2015.1040388

http://scihub22266oqcxt.onion/10.1517/14740338.2015.1040388
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C6053318!6053318!25912929
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suck abstract from ncbi


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pmid25912929      Expert+Opin+Drug+Saf 2015 ; 14 (7): 1055-70
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  • Everolimus and Sirolimus in Transplantation-Related but Different #MMPMID25912929
  • Klawitter J; Nashan B; Christians U
  • Expert Opin Drug Saf 2015[Jul]; 14 (7): 1055-70 PMID25912929show ga
  • Introduction: The inhibitors of the mammalian target of rapamycin (mTOR) sirolimus and everolimus are used as immunosuppressants after organ transplantation in combination with calcineurin inhibitors, but also as proliferation signal inhibitors coated on drug eluting stents and in cancer therapy. Notwithstanding their related chemical structures both have distinct pharmacokinetic, pharmacodynamic and toxicodynamic properties. Areas covered: The additional hydroxyethyl group at the C(40) of the everolimus molecule results in different tissue and subcellular distribution, different affinities to active drug transporters and drug metabolizing enzymes as well as differences in drug-target protein interactions including a much higher potency in terms of interacting with the mTOR complex 2 (mTORC2) than sirolimus. Said mechanistic differences as well as differences found in clinical trials in transplant patients are reviewed. Expert opinion: In comparison to sirolimus, everolimus has higher bioavailability, a shorter terminal half-life, different blood metabolite patterns, the potential to antagonize the negative effects of calcineurin inhibitors on neuronal and kidney cell metabolism (which sirolimus enhances), the ability to stimulate mitochondrial oxidation (which sirolimus inhibits), and to reduce vascular inflammation to a greater extent. A head-to-head, randomized trial comparing the safety and tolerability of these two mTOR inhibitors in solid organ transplant recipients is merited.
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