Effects of the immune system on cyclosporine absorption

1. The pharmacokinetics and toxicodynamics of single and multiple doses of cyclosporine were studied in the immunized rat model and compared with non-immunized rats. 2. The pharmacokinetics of cyclosporine i.v. (5 mg/kg per day) were similar in immunized and non-immunized rats after single or multiple doses. 3. The absolute bioavailabilities of single and multiple doses of cyclosporine (10 mg/kg per day) given orally were significantly decreased in immunized rats compared with non-immunized rats. 4. Oral administration of cyclosporine (10 mg/kg per day) did not alter renal function of non-immunized rats compared with untreated controls. However, inulin clearance decreased greater than four-fold in immunized rats given cyclosporine for 7 days. 5. In summary, the pharmacokinetics and toxicodynamics of cyclosporine given orally to rats are affected by the immune system.