[Kinetic distribution of cyclosporine after single dose subcutaneous administration; experimental study in rats]

Adequate dose of cyclosporin A shows immunosuppressor effect, and low toxicity. The doses reported previously ranged from 2.5 to 25 mg/kg every 24, 48 hours and even 7 days. Routes for cyclosporin A administration are subcutaneous or intramuscular preferentially. In the present study, cyclosporin A (CSA) single dose subcultaneous was administered to 21 Wistar-Furth rats, adult, males, weighing 350-450g. The animals were divided in 3 groups receiving 2.5 mg/kg (group 1), 5.0 mg/kg (group 2) and 10.0 mg/kg (group 3). Blood samples were collected at 1, 4, 8, 12, 24, 48 and 72 hours after drug collection into plastic tubes containing sodium EDTA. Blood cyclosporin A levels were determined by a commercially available radioimmunoassay kit (Sandoz RIE Kit Basel) after whole hemolysis using liquid nitrogen. Cyclosporin A blood concentrations vs time curve were plotted (log C vs t). Two compartment open model was applied to estimate the kinetic parameters as t(1/2) beta e beta. A model independent calculation was applied to estimate the kinetic parameters as AUCT, CIT and Vd. Initially, parametric and nonparametric tests were applied. Due to the high dispositional variability, nonparametric statistics (Wilcoxon's test) was applied for analysis of results obtained. Based on data obtained in the present study the authors suggest linear pharmacokinetics where Cmax AUCT showed proportional increases with the dose administered, remaining unchanged the Kinetic parameters as t(1/2) B,B, CIT and Vd.