A. Ibarra et al., ALTERATION OF CYCLOSPORINE-A PHARMACOKINETICS AFTER EXPERIMENTAL SPINAL-CORD INJURY, Journal of neurotrauma, 13(5), 1996, pp. 267-272
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.