Bohdanecká M, Schück O, Petrásek R, Sedivý J, Reitschlägerová V
Nefrologická klinika, Centrální izotopové pracovistĕ, Klinika diabetologie a Interní katedra Institutu klinické a experimentální medicíny, Praha.
Cas Lek Cesk. 1994 Jul 18;133(14):434-7.
The aim of the study was to determine whether or not uraemia has an effect on cyclosporine A intestinal resorption.
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.
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.
本研究的目的是确定尿毒症是否对环孢素A的肠道吸收有影响。
在大鼠身上进行模型实验,以监测急性尿毒症(双侧肾切除术)对环孢素A动力学的影响。通过胃管,以Consupren(捷克共和国Galena公司)的形式给一组大鼠施用环孢素A,以Sandimmune(瑞士山德士公司)的形式给另一组大鼠施用环孢素A,两种情况下剂量均为10mg/kg/24h。使用放射免疫分析法以及特异性和非特异性抗体(环孢素及其代谢物)测定环孢素A的血药浓度。将肾切除大鼠的环孢素A动力学与对照大鼠以及接受假肾切除手术的大鼠进行比较。肾切除大鼠中环孢素A的血药浓度显著较低,且其血药浓度曲线下面积(AUC)明显小于对照大鼠。使用Consupren或Sandimmune后,所评估参数未观察到显著差异。
我们的研究结果支持尿毒症会降低环孢素A有效性这一假说。结果表明,肾切除大鼠在施用Consupren和Sandimmune后环孢素A动力学的变化具有相同特征。