Acute Spinal Cord Injury Alters the Bioavailability of Oral and Intraperitoneal Cyclosporine-A in Contused Rats

Pharmacokinetics (PK) of drugs such as gentamicin and theophylline is altered in humans with spinal cord (SC) injury (Segal, 1985). These observations led us to suspect that the PK of cyclosporine-A (CsA) might be altered in experimental SC injury. Our goal was to establish the best immunosuppressive strategy with CsA for our rat model of traumatic SC injury, in order to control the autoimmune response seen after trauma and to control the immune response to tissue grafts in transplanted SC-lesioned rats. We determined the PK of CsA, administered in a single dose of 10 mg/kg b.w., in three groups of 10 rats each, as follows: Group A: acutely SC-lesioned rats. Five rats were given the drug orally and five received the drug intraperitoneally one day after injury. Group B: chronically SC-lesioned rats. Five rats were given CsA orally and five received the drug intraperitoneally 7-9 weeks after injury. Group C: sham-lesioned rats. Five rats were given CsA orally and five received the drug intraperitoneally one day after laminectomy. Blood samples were collected from the tail of each anesthetized rat before and 2, 4, 6, 12 and 24 hours after drug administration. The serum levels of CsA were determined by RIA, and the PK parameters assessed were: maximum serum concentration (Cmx), time to reach maximum serum concentration (tmax) and area under the