TY - JOUR
T1 - An evaluation of sirolimus in renal transplantation
AU - Halleck, Fabian
AU - Duerr, Michael
AU - Waiser, Johannes
AU - Huber, Lu
AU - Matz, Mareen
AU - Brakemeier, Susanne
AU - Liefeldt, Lutz
AU - Neumayer, Hans Hellmut
AU - Budde, Klemens
N1 - Funding Information:
M Duerr has received honoraria from Bristol-Myers Squibb. J Waiser has received honoraria from Novartis Pharma AG and M Matz has received a research grant from Novartis Pharma AG. L Liefeldt received honoraria/grant from Novartis Pharma AG while H-H Neumayer has received research grants and honoraria from Novartis Pharma AG, Bristol-Myers Squibb, Roche, Pfizer and Astellas. K Budde has received research grants and/or honoraria from AiCuris, Astellas, Bristol-Myers Squibb, Hexal, Novartis Pharma, Pfizer, Roche AG, Siemens AG, TCL Pharma und Veloxis Pharma. The other authors declare no conflicts of interest.
PY - 2012/10
Y1 - 2012/10
N2 - Introduction: Sirolimus is a powerful antiproliferative immunosuppressive drug approved for the prevention of kidney allograft rejection. By its unique mechanism of action, sirolimus provides a multitude of clinical potential and has been used effectively in different drug combinations. Extensive experience has been gained regarding the best timing of its application, side effect profile and potential benefits and limitations compared with other immunosuppressive drugs. Areas covered: The authors evaluate the recent experience with sirolimus in kidney transplantation. Pivotal randomized controlled trials were used to provide an overview with special attention to pharmacokinetic and dynamic aspects of sirolimus, its current clinical use as well as perspectives for its future role. Expert opinion: Sirolimus enriches the possibilities of immunosuppressive therapies after renal transplantation. Beneficial effects toward kidney function by allowing CNI sparing, lower incidence of malignancies and less viral infections have been suggested. Sirolimus should be used cautiously in de novo patients for reasons of wound healing. An early conversion to a sirolimus-based CNI-free regimen has shown promising results, whereas late conversion is more challenging. Finally, sirolimus-associated side effects are causing tolerability concerns and frequent discontinuations. Future research should aim to better define the therapeutic window and those patients most likely to benefit.
AB - Introduction: Sirolimus is a powerful antiproliferative immunosuppressive drug approved for the prevention of kidney allograft rejection. By its unique mechanism of action, sirolimus provides a multitude of clinical potential and has been used effectively in different drug combinations. Extensive experience has been gained regarding the best timing of its application, side effect profile and potential benefits and limitations compared with other immunosuppressive drugs. Areas covered: The authors evaluate the recent experience with sirolimus in kidney transplantation. Pivotal randomized controlled trials were used to provide an overview with special attention to pharmacokinetic and dynamic aspects of sirolimus, its current clinical use as well as perspectives for its future role. Expert opinion: Sirolimus enriches the possibilities of immunosuppressive therapies after renal transplantation. Beneficial effects toward kidney function by allowing CNI sparing, lower incidence of malignancies and less viral infections have been suggested. Sirolimus should be used cautiously in de novo patients for reasons of wound healing. An early conversion to a sirolimus-based CNI-free regimen has shown promising results, whereas late conversion is more challenging. Finally, sirolimus-associated side effects are causing tolerability concerns and frequent discontinuations. Future research should aim to better define the therapeutic window and those patients most likely to benefit.
KW - Calcineurin inhibitors
KW - Kidney transplantation
KW - MTOR inhibitors
KW - Rapamycin
KW - Sirolimus
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U2 - 10.1517/17425255.2012.719874
DO - 10.1517/17425255.2012.719874
M3 - Article
C2 - 22928953
AN - SCOPUS:84866524136
SN - 1742-5255
VL - 8
SP - 1337
EP - 1356
JO - Expert Opinion on Drug Metabolism and Toxicology
JF - Expert Opinion on Drug Metabolism and Toxicology
IS - 10
ER -