Central nervous system pharmacokinetics of high-dose cytosine arabinoside.
The cerebrospinal fluid (CSF) pharmacokinetics of cytosine arabinoside (Ara-C) was determined in 8 patients with metastatic cancer in the central nervous system. High dose (3 gm/M2) one-hour intravenous infusions of Ara-C were given with serial CSF sampling obtained from indwelling Ommaya reservoirs. CSF was analyzed by high pressure liquid chromatography. Mean Ara-C elimination half life of 140 minutes in CSF was eight times longer than that in plasma. The peak mean CSF concentration of Ara-C (2.1 micrograms /ml) was about 7% of the plasma concentration (30 micrograms/ml). A total of 28 treatment courses were administered with minimal hematopoietic, gastrointestinal and neurological toxicities. A schedule of administration of 2 high-dose treatments 12 hours apart repeated every two weeks should maintain cytotoxic CSF concentrations which could prove useful in the management of CNS leukemia and lymphoma.
D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000097:blood / Q000134:cerebrospinal fluid / Q000556:secondary*; D002851:Chromatography, High Pressure Liquid; D003561:Cytarabine / Q000097:blood / Q000134:cerebrospinal fluid*; D005260:Female; D006801:Humans; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D013997:Time Factors
D003561:Cytarabine