A. Ibarra et al., USE OF CYCLOSPORINE-A IN EXPERIMENTAL SPINAL-CORD INJURY - DESIGN OF A DOSING STRATEGY TO MAINTAIN THERAPEUTIC LEVELS, Journal of neurotrauma, 13(10), 1996, pp. 569-572
Cyclosporin-A (CsA) is frequently used as an immunosuppressive agent i
n experimental transplantations. CsA has been used in nervous tissue t
ransplants in spinal cord injury (SCI). However, optimal results have
not been obtained. This is likely due to the fact that SCI alters CsA
pharmacokinetics and hence fixed dose regimens are not adequate. In th
is study, several CsA dosing regimens were evaluated in Long-Evans fem
ale rats subjected to a severe low thoracic (T8) SCI by the contusion
method. Serum CsA concentrations were measured to determine which dosi
ng regimen allowed CsA levels to be maintained within the therapeutic
window. It was found that administration of 2.5 mg/kg/12 h intraperito
neally during the first 2 days after SCI (acute phase) followed by 5 m
g/kg/12 h orally thereafter (subacute and chronic phases) yields CsA c
irculating levels within the therapeutic window, i.e., 0.120-0.275 mu
g/mL. This dosing regimen represents a suitable alternative to fixed d
osing to achieve an optimal CsA-induced immunosuppression in experimen
tal models of SCI.