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.
Bronster
D J
DJ
The Recanati/Miller Transplantation Institute and Department of Pharmacy, The Mount Sinai Medical Center, New York, New York 10029, USA.
Chodoff
L
L
Yonover
P
P
Sheiner
P A
PA
D000328:Adult; D001806:Blood Urea Nitrogen; D016572:Cyclosporine / Q000009:adverse effects / Q000134:cerebrospinal fluid*; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000134:cerebrospinal fluid*; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies
D007166:Immunosuppressive Agents; D016572:Cyclosporine