Prolongation Of Renal Allograft Survival In A Large Animal Model By Oral Rapamycin Monotherapy

Sirolimus (rapamycin, Rapamune ® ) and combination therapy with cyclosporin A in the rat developing adjuvant arthritis model: Correlation with blood levels and the effects of different oral formulations

“…Combinational therapy of sirolimus and CsA at low doses in animal transplantation experiments has demonstrated reduced renal toxicity [15,18]. In this regard, the reduction in toxicity of sirolimus that we observed in rat adjuvant arthritis model when using non-daily combinational 342 R. P. Carlson et al…”

“…In transplantation animal models, trough blood levels of sirolimus of 5-10 ng/ml produced maximum therapeutic effects (i.e. prolongation of allografts in rat, rabbit, dog and pig) [14][15][16][17][18] and trough levels as low as 0.5 ng/ml of sirolimus produced measurable effects in the porcine renal allograft model [18]. The combination dosing regimens of sirolimus and CsA in mice [19,20], in rat [21,22] and dog [17] produced pharmacologically synergistic activities possibly due to their different mechanisms of actions (i.e.…”

Crossing the bridge: large animal models in translational transplantation research

“…Rapamycin monotherapy prolongs MHC disparate swine renal allograft survival to a degree comparable to that of triple immunosuppression with cyclosporine, azathioprine, and prednisone, resulting in a mean survival of 60 days (59, 60). Unlike calcineurin inhibitors, rapamycin has not been shown to induce tolerance in swine renal allograft models.…”

The effects of drugs with immunosuppressive or immunomodulatory activities on xenobiotics-metabolizing enzymes expression in primary human hepatocytes

“…95% presence in erythrocytes, remaining fractions are distributed among plasma, lymphocytes and granulocytes (Yatscoff et al, 1995). Studies in animals and humans indicated that immunosuppressive doses of sirolimus are those where whole blood concentrations are within the range of 5-30 ng/mL (Granger et al, 1995;Honcharik et al, 1992). In vitro, sirolimus is CYP3A substrate in rat as well as in human liver microsomes (Sattler et al, 1992) and it is a substrate for P-gp as well (Lampen et al, 1998).…”