TY - JOUR
T1 - Use of cyclosporin-A in experimental spinal cord injury
T2 - Design of a dosing strategy to maintain therapeutic levels
AU - Ibarra, Antonio
AU - Reyes, Julián
AU - Martínez, Simón
AU - Correa, Dolores
AU - Guízar-Sahagún, Gabriel
AU - Grijalva, Israel
AU - Castañeda-Hernández, Gilberto
AU - Flores-Murrieta, Francisco J.
AU - Franco-Bourland, Rebecca
AU - Madrazo, Ignacio
PY - 1996/1/1
Y1 - 1996/1/1
N2 - Cyclosporin-A (CsA) is frequently used as an immunosuppressive agent in experimental transplantations. CsA has been used in nervous tissue transplants 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 this study, several CsA dosing regimens were evaluated in Long-Evans female rats subjected to a severe low thoracic (TS) SCI by the contusion method. Serum CsA concentrations were measured to determine which dosing regimen allowed CsA levels to he maintained within the therapeutic window. It was found that administration of 2.5 mg/kg/12 h intraperitoneally during the first 2 days after SCI (]acute phase) followed by 5 mg/kg/12 h orally thereafter (subacute and chronic phases) yields CsA circulating levels within the therapeutic window, i.e., 0.120-0.275 μg/mL. This dosing regimen represents a suitable alternative to fixed dosing to achieve an optimal CsA-induced immunosuppression in experimental models of SCI.
AB - Cyclosporin-A (CsA) is frequently used as an immunosuppressive agent in experimental transplantations. CsA has been used in nervous tissue transplants 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 this study, several CsA dosing regimens were evaluated in Long-Evans female rats subjected to a severe low thoracic (TS) SCI by the contusion method. Serum CsA concentrations were measured to determine which dosing regimen allowed CsA levels to he maintained within the therapeutic window. It was found that administration of 2.5 mg/kg/12 h intraperitoneally during the first 2 days after SCI (]acute phase) followed by 5 mg/kg/12 h orally thereafter (subacute and chronic phases) yields CsA circulating levels within the therapeutic window, i.e., 0.120-0.275 μg/mL. This dosing regimen represents a suitable alternative to fixed dosing to achieve an optimal CsA-induced immunosuppression in experimental models of SCI.
KW - cyclosporin A
KW - dosing regimen
KW - pharmacokinetics
KW - spinal cord injury
KW - spinal cord transplantation
UR - http://www.scopus.com/inward/record.url?scp=10344265037&partnerID=8YFLogxK
U2 - 10.1089/neu.1996.13.569
DO - 10.1089/neu.1996.13.569
M3 - Artículo
C2 - 8915908
AN - SCOPUS:10344265037
SN - 0897-7151
VL - 13
SP - 569
EP - 572
JO - Journal of Neurotrauma
JF - Journal of Neurotrauma
IS - 10
ER -