PGE2 reduces nephrotoxicity and immunosuppression of cyclosporine in rats

Acute cyclosporine nephrotoxicity is characterized by the dose-dependent reduction of glomerular filtration rate both in patients and experimental animals. Administration of a vasodilator agent such as PGE2 might prevent glomerular vasoconstriction and hence reduce cyclosporine nephrotoxicity. The results of the present investigation in spontaneously hypertensive rats indicate that a synthetic PGE2 prevents cyclosporine nephrotoxicity. Pharmacokinetic studies revealed that CSA plasma peak levels and area under the plasma concentration-time curve were significantly decreased in PGE2 treated rats, indicating reduced bioavailability of oral CSA. Furthermore, the immunosuppressive effect of CSA was completely abolished by concomitant PGE2 administration. In summary, the preventive effect of a synthetic PGE2 analogue on CSA nephrotoxicity in rats is most likely due to a reduced enteral absorption of CSA, resulting in insufficient immunosuppression.