Use of cyclosporin-A in experimental spinal cord injury: design of a dosing strategy to maintain therapeutic levels.
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 (T8) SCI by the contusion method. Serum CsA concentrations were measured to determine which dosing regimen allowed CsA levels to be 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 microgram/mL. This dosing regimen represents a suitable alternative to fixed dosing to achieve an optimal CsA-induced immunosuppression in experimental models of SCI.
Proyecto CAMINA, A.C., México, D.F.
A
A
Ibarra
J
J
Reyes
S
S
Martínez
D
D
Correa
G
G
Guízar-Sahagún
I
I
Grijalva
G
G
Castañeda-Hernández
F J
FJ
Flores-Murrieta
R
R
Franco-Bourland
I
I
Madrazo
D000818:Animals; D016572:Cyclosporine / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D005260:Female; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D007274:Injections, Intraperitoneal; D051381:Rats; D013116:Spinal Cord / Q000637:transplantation; D013119:Spinal Cord Injuries / Q000188:drug therapy*
D007166:Immunosuppressive Agents; D016572:Cyclosporine