Dissolving intravenous cyclosporin A in a fat emulsion carrier prevents acute renal side effects in the rat.
Cyclosporin A (CyA)-induced nephrotoxicity is still a serious clinical problem. The nephrotoxicity seems to be more pronounced when CyA (solubilized in water with Cremophore EL, as in Sandimmun) is given intravenously than when it is given orally. Using soybean oil in which CyA was dissolved, we prepared an intravenous fat emulsion without an artificial detergent, such as Cremophore EL. The renal effects of our new formula were compared with those of Sandimmun and Cremophore EL in a rat model. CyA in the fat emulsion did not significantly affect the glomerular filtration rate (GFR). Both Sandimmun and Cremophore EL significantly reduced the GFR. These results suggest that a change in the vehicle may obviate the acute nephrotoxic side effects caused by intravenous administration of CyA solubilized by Cremophore EL.
Tibell
A
A
Department of Transplantation Surgery, Huddinge Hospital, Sweden.
Larsson
M
M
Alvestrand
A
A
D000818:Animals; D016572:Cyclosporine / Q000008:administration & dosage / Q000633:toxicity*; D004337:Drug Carriers; D004655:Emulsions; D005919:Glomerular Filtration Rate / Q000187:drug effects; D005990:Glycerol / Q000008:administration & dosage / Q000031:analogs & derivatives; D007262:Infusions, Intravenous; D007668:Kidney / Q000187:drug effects*; D007674:Kidney Diseases / Q000139:chemically induced / Q000517:prevention & control*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012995:Solubility; D013024:Soybean Oil
D004337:Drug Carriers; D004655:Emulsions; C000515:cremophor EL; D013024:Soybean Oil; D016572:Cyclosporine; D005990:Glycerol