Digestive Diseases and Sciences
The new immunosuppressive agent sirolimus is combined in transplant patients with the cholestatic substances cyclosporin and tacrolimus. Nothing is known about possible cholestatic effects of these combinations. Therefore, we compared their effects on bile flow and on important bile parameters in an acute bile fistula model in rats. Cyclosporin red...
British journal of pharmacology
Clinical studies have shown enhancement of cyclosporine toxicity when co-administered with the immunosuppressant sirolimus. We evaluated the biochemical mechanisms underlying the sirolimus/cyclosporine interaction on rat brain metabolism using magnetic resonance spectroscopy (MRS) and compared the effects of sirolimus with those of the structurally...
Biochemical and Biophysical Research Communications
We have identified an 8.4 kDa minor immunophilin from calf thymus and Jurkat T cells as ubiquitin. It binds tacrolimus and sirolimus with K d's of 0.8 and 0.08 nM, respectively. The binding of this protein to cyclosporin A is negligible. Binding of tacrolimus to two commercial sources of ubiquitin, a bovine product, and a recombinant human ubiquiti...
Purpose. To assess pharmacokinetic and pharmacoimmunodynamic interactions between prednisolone (Pred, 1 mg/kg) and sirolimus (Sir, 0.25 mg/kg) in rabbits. Methods. After intravenous administration, plasma concentrations of Pred and corticosterone, and Sir blood concentrations were followed for 24 hours along with blood granulocyte and T-helper cell...
Clinical and experimental immunology
The studies presented herein examined the mechanism(s) whereby sirolimus (SRL) and cyclosporin (CsA) act synergistically to block allograft rejection. Combination index (CI = 1 reflects additive, CI > 1 antagonistic, and CI