Cyclosporine levels in cerebrospinal fluid after liver transplantation

Background. The mechanisms underlying cyclosporine neurotoxicity remain undefined. Particularly, whether cyclosporine (CyA) enters cerebrospinal fluid (CSF) or brain tissue is disputed. Methods. We analyzed CSF from 17 lumbar punctures performed in 14 liver recipients receiving CyA and experiencing neurological complications, fever of unknown origin, seizures, or altered mental status. Whole blood samples were assayed for CyA and its metabolites. Liver function tests, serum electrolytes, and cholesterol were also analyzed. Results. Four patients had cyclosporine metabolites in the CSF. These patients had acute renal insufficiency and significantly higher blood urea nitrogen (BUN) and total and direct bilirubin and alkaline phosphatase levels than patients without CyA metabolites in CSF (P <0.05). Whole blood levels of CyA parent drug were similar between groups. Levels of CyA metabolites in the blood were significantly higher in patients with metabolites in the CSF. CyA parent drug was undetectable in CSF in both groups. Conclusions. This is the first prospective report of CyA metabolites in the CSF of transplant recipients. Acute renal insufficiency and high bilirubin levels may be associated with entry of CyA metabolites into the CSF.