Combination treatment with sirolimus and ciclosporin in clinical renal transplantation: A comprehensive review

Sirolimus is a potent new immunosuppressive agent that has been shown to re duce the incidence of acute rejection episodes among renal transplant recip ients as well as provide a unique approach to optimize treatment outcomes i n difficult transplant situations. Owing to its properties as a critical-do se drug, therapeutic concentration monitoring of sirolimus readily compensa tes for intra- and interpatient variability and drug interactions with a va riety of other agents such as ciclosporin. This review summarizes the resul ts that demonstrate the efficacy of sirolimus in combination treatment with ciclosporin in human renal transplantation, as well as its potential in al ternative therapeutic modalities in a broad range transplant recipients. Th e clinical trials for SDZ-RAD, a macrocyclic lactone immunosuppressant stru cturally similar to sirolimus, also are reviewed herein. SDZ-RAD was develo ped in an attempt to improve the pharmacokinetic characteristics of sirolim us, particularly to increase the extent and reproducibility of its oral bio availabillty and to reduce the extensive tissue distribution by virtue of i ts greater polarity. (C) 2001 Prous Science. All rights reserved.