PMID: 6977672Mar 1, 1982Paper

Cerebrospinal fluid levels of 2'-deoxycoformycin after systemic administration in monkeys

Journal of the National Cancer Institute
J BlattD G Poplack

Abstract

2'-Deoxycoformycin (DCF) is an inhibitor of the enzyme adenosine deaminase (ADA) and has shown promise as an antileukemia agent. For the assessment of the extent to which systemically administered DCF crosses into the central nervous system (CNS), rhesus monkeys were given iv boluses of DCF. Simultaneous blood and cerebrospinal fluid (CSF) samples were assayed for DCF levels at times ranging from 10 minutes to 6 hours after the drug was given. Average peak CSF drug levels of 5.5 X 10(-8) M and 3 X 10(-7) M were reached 1 1/2 - 2 hours following injections of 0.25 and 1.0 mg DCF/kg, respectively. The ratio of peak CSF to simultaneous plasma levels was 1 to 10. Data obtained from a patient who had acute lymphocytic leukemia and who was given iv DCF were comparable. Drug levels achieved within the CSF following iv administration of 0.25 mg DCF/kg are similar to those previously demonstrated to inhibit ADA. These results may be important both for understanding DCF-related CNS toxicity and for designing combination chemotherapy with DCF.

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