Effect of Streptozotocin-Induced Diabetes on Cyclosporin A Disposition in Rats

概要

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We studied the effect of diabetes on the pharmacokinetics of cyclosporin A (CyA) after intravenous and oral administration of CyA using the plasma and lymph of streptozotocin (STZ)-induced diabetic rat. There were no significant differences in the systemic and lymphatic availabilities after intravenous administration of CyA in diabetic rats compared with those of the controls. On the other hand, systemic and lymphatic availabilities after oral administration of CyA were significantly different in diabetic rats compared to those in the controls. These results suggest that the pharmacokinetics of CyA, particularly absorption, were altered in diabetic rats. Gastrointestinal transit in diabetic rats was also studied. The gastric emptying rate in diabetic rats was enhanced compared with that of the controls, but small intestinal transit was reduced in diabetic rats, suggesting that a change in gastro-intestinal transit in diabetic rats may influence the absorption of CyA.The increased absorption of CyA from the digestive tract of diabetic rats altered not only the systemic availability but also the lymphatic availability, suggesting that altered systemic availability may cause adverse effects and that altered lymphatic availability may influence the immunosuppressive effects.
公益社団法人日本薬学会の論文
1996-12-15