650 High Rate of Discontinuation of a Mammalian Target of Rapamycin Inhibitor Based Regime during Long-Term Follow-Up of Cardiac Transplant Recipients

González‐Costello, José; Kaplinsky, Edgardo; Manito, Nicolás; Roca, Joan; Nebot, M. Simó; Barbosa, M.J.; Mañas, Pilar; Salazar, Jorge Brenes; Cequier, Ángel

doi:10.1016/j.healun.2012.01.664

Cited by 1 publication

(1 citation statement)

References 6 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Moreover, everolimus showed significantly better survival without edema or infections and only sirolimus treatment was shown to be an independent predictor of adverse events [75]. However, in a larger retrospective study of 409 maintenance kidney transplant patients converted to mTOR inhibition, a numerically higher rate of discontinuation with everolimus (31.4%) versus sirolimus (22.8%, p=0.051) was observed [76]. It should be noted that in these studies there were too many uncontrolled variables to allow for a firm conclusion including, but not limited to, the concomitant immunosuppression regimen, the year of transplantation and immunosuppressant exposure levels.…”

Section: Comparison Of Sirolimus and Everolimus In Clinical Trialsmentioning

confidence: 99%

Everolimus and sirolimus in transplantation-related but different

Klawitter

Nashan

Christians

2015

Expert Opinion on Drug Safety

156

109

View full text Add to dashboard Cite

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.

show abstract

Section: Comparison Of Sirolimus and Everolimus In Clinical Trialsmentioning

confidence: 99%