Effect of streptozotocin-induced diabetes on cyclosporin A disposition in rats.
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 gastrointestinal 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.
Ogata
M
M
Department of Pharmaceutics, Tohoku College of Pharmacy, Sendai, Japan.
Iizuka
Y
Y
Murata
R
R
Hikichi
N
N
D000284:Administration, Oral; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D016572:Cyclosporine / Q000097:blood / Q000493:pharmacokinetics*; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000378:metabolism*; D005746:Gastric Emptying / Q000502:physiology; D005772:Gastrointestinal Transit / Q000502:physiology; D007166:Immunosuppressive Agents / Q000097:blood / Q000493:pharmacokinetics*; D007275:Injections, Intravenous; D007408:Intestinal Absorption; D008208:Lymphatic System / Q000378:metabolism; D008297:Male; D051381:Rats; D017208:Rats, Wistar
D001786:Blood Glucose; D007166:Immunosuppressive Agents; D016572:Cyclosporine