糖尿病モデルラットにおけるシクロスポリンAの腸管吸収

概要

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Cyclosporin A (CyA), an immunosuppressant drug, is widely used in the treatment of kidney transplantation in severe diabetic patients. The drug has a clinical problem because of its variable oral bioavailability between patients and even within the same patient. We investigated the effects of diabetic disease models on the absorption of CyA from three parts of small intestine in streptozotocin-induced diabetic (STZ) rats and non-obese spontaneous Goto-Kakizaki (GK) rats. The intestinal absorption rate evaluated by the in situ loop method showed that the remaining rate in the loop was higher in both diabetic model rats, especially in the ileum of STZ rats, than that in control rats. The increased remaining rate was markedly depressed by the addition of verapamil, a well-known specific inhibitor of P-glycoprotein (P-gp). Western blot analysis using monoclonal antibody against P-gp, C219, was carried out : An increased P-gp expression in the intestines was shown in the two diabetic model rats compared with the control rats, being in good agreement with the in situ absorption data. These results suggested the possibility of decreased intestinal absorption of CyA due to the increased expression of P-gp in the diabetic disease.
東北薬科大学の論文