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| - Cyclosporin A in fat emulsion carriers: studies on the immunosuppressive potential, using the heterotopic heart transplant model in rats
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| - Abstract. Cyclosporin A (CyA) is an extremely lipophilic drug that needs a solubilizing agent to become soluble in water. In the commercially available intravenous formulation-Sandimmun-Cremophor EL is used for this purpose. It is likely that Cremophor EL contributes to some of the side effects produced by i. v. Sandimmun. We have recently shown that if Cremophor EL is replaced by a soybean oil (SBO)-based fat emulsion carrier, the acute renal side effects following i. v. administration of CyA are avoided in a rat model. It is then important to ascertain whether the use of a fat emulsion carrier alters the immunosuppressive effect of CyA. Moreover, fatty acids can themselves influence the immune system, and both omega-3 and omega-6 fatty acids have been reported to possess immunosuppressive properties. In the present study, the effect on graft survival of i. v. CyA administered in five different formulations, using fat emulsions or liposomes as carriers, was compared to that of conventional Sandimmun infusion substance in the heterotopic heart transplant model in rats. The new formulations tested did not reduce the immunosuppressive effect of CyA. On the contrary, a small but significant increase in graft survival was noted in the groups given CyA in the SBO-based fat emulsion carrier (17.0±0.82 days) and CyA in liposomes (16.0±0.63 days) as compared to the results in the Sandimmun-treated group (15.0±0.58 days: P<0.01 and P<0.05, respectively).
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