Deoxycoformycin: neurological toxicity

Deoxycoformycin (DCF) is a tight-binding inhibitor of adenosine deaminase (ADA) currently undergoing phase I--II evaluation. Neurological toxicity has been a frequent and occasionally severe complication of treatment with this drug. A T-cell leukemia patient with an Ommaya reservoir was treated with DCF, and the pharmacokinetics of the drug in the cerebrospinal fluid and plasma were studied. DCF penetrates the cerebrospinal fluid and achieves levels as high as 1/10 the concurrent plasma levels. The accumulation of adenosine and deoxyadenosine in plasma, cerebrospinal fluid, and urine was monitored; the neuropharmacological effect of these metabolites is discussed.