Aims To evaluate the tolerability of single oral SDZ RAD doses in stable renal transplant recipients and the pharmacokinetics of ascending SDZ RAD doses when coadministered with steady-state cyclosporin A microemulsion (Neoral). Methods This randomized, double-blind, placebo-controlled, sequential study involved 54 patients in six treatment groups; a different SDZ RAD dose (0.25, 0.75, 2.5, 7.5, 15, 25 mg ) was assessed in each group. Patients received a single oral dose of SDZ RAD (n=6) or placebo (n=3) with their usual Neoral dose. SDZ RAD and cyclosporin A pharmacokinetic parameters were determined. Results All SDZ RAD doses were well tolerated, with no discontinuations due to adverse events, serious adverse events, or deaths. Similar proportions of patients receiving SDZ RAD and placebo had at least one adverse event (44% and 50%, respectively). Mean changes in laboratory variables (baseline to endpoint) showed no clinically meaningful differences between SDZ RAD and placebo groups. SDZ RAD was absorbed rapidly and showed dose-proportional pharmacokinetics (dose: 2.5-25 mg), based on systemic exposure. Multiple postabsorptive phases in the pharmacokinetic profile indicate tissue distribution. The elimination half-life ranged from 24 to 35 h across the five highest dose groups. Pharmacokinetics were similar in men and women. Co-administration of escalating single oral SDZ RAD doses did not affect steady-state cyclosporin A pharmacokinetics. Conclusions SDZ RAD was well tolerated; safety profiles of SDZ RAD and placebo were similar. SDZ RAD pharmacokinetics were dose-proportional across the range 2.5-25 mg in conjunction with cyclosporin A-based therapy, according to systemic exposure. Cyclosporin A pharmacokinetics were not affected by coadministration of single oral doses of 0.25-25 mg SDZ RAD.Keywords: cyclosporin A, immunosuppressant, pharmacokinetics, safety, SDZ RAD, transplantation 40. This modification allowed the development of a solid Introduction dosage formulation that is more convenient to administer than rapamycin, which must be prepared from a The immunosuppressive properties of rapamycin have been known for more than 15 years [1, 2], but the refrigerated stock solution just before use. SDZ RAD has a mechanism of action similar to that of rapamycin: clinical development of the drug has been hampered by its limited oral bioavailability. A novel immunoinhibition of growth factor-driven proliferation of T cells and fibroblasts. SDZ RAD prevents graft rejection in rat suppressant, SDZ RAD, has recently been developed. SDZ RAD is a derivative of rapamycin but differs models of allotransplantation (kidney, heart) [3]. SDZ RAD and cyclosporin A show synergism in immunostructurally by having a 2-hydroxyethyl chain at position suppression both in vitro and in vivo [4].