ALTERATION OF CYCLOSPORINE-A PHARMACOKINETICS AFTER EXPERIMENTAL SPINAL-CORD INJURY

The pharmacokinetics of the immunosuppressive agent cyclosporin-A (CsA ) were studied in rats submitted to spinal cord (SC) injury, A single CsA 10 mg/kg dose was given either intraperitoneally (ip) or orally to rats submitted to experimental SC injury at the TS level, Twenty four hours after lesion (acute stage of SC injury) ip CsA bioavailability was increased, while t(1/2) was prolonged, However, oral bioavailabili ty was reduced, Seven weeks after lesion (chronic stage of SC injury) CsA bioavailability, by either route, was not significantly different from control values, Results indicate that parenteral CsA bioavailabil ity is increased during the acute stage of SC lesion, probably due to an impaired elimination, Oral bioavailability, however, is decreased, since there is also an important reduction in gastrointestinal CsA abs orption that overrides the effect of impaired elimination, Alterations in CsA pharmacokinetics appear to revert during the chronic stage of SC injury. Changes in CsA bioavailability, depending on the route of a dministration and on time, must be considered to design an adequate im munosuppressive treatment in SC injury.