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[An experimental model of the effect of uremia on cyclosporin A availability]
M Bohdanecká1, O Schück, R Petrásek
1Nefrologická klinika, Centrální izotopové pracovistĕ, Klinika diabetologie a Interní katedra Institutu klinické a experimentální medicíny, Praha.
Background:
The aim of the study was to determine whether or not uraemia has an effect on cyclosporine A intestinal resorption.
Methods And Results:
Model experiments were conducted in rats to monitor the effect of acute uraemia (bilateral nephrectomy) on the kinetics of cyclosporine A. Using intragastric tube, Cyclosporine A was administered to one group of rats in the form of Consupren (Galena, Czech Republic) and to another group in the form of Sandimmune (Sandoz, Switzerland), at a dose of 10 mg/kg/24 h either case. Blood levels of cyclosporine A were determined using RIA and specific and non-specific antibodies (cyclosporine and its metabolites). Cyclosporine A kinetics in nephrectomized rats was compared with that in control rats and in rats undergoing sham nephrectomy. The blood levels of cyclosporine A were significantly lower, and the area under the curve (AUC) of blood cyclosporine A in nephrectomized rats significantly smaller than in control rats. No significant differences in the evaluated parameters after Consupren or Sandimmune were observed.
Conclusions:
Our findings support the hypothesis that uraemia decreases cyclosporine A availability. The results suggest that the changes in cyclosporine A kinetics in nephrectomized rats following Consupren and Sandimmune administration are of the same character.