2-Chloro-2'-deoxyadenosine--clinical, biochemical and pharmacokinetic considerations

2-Chloro-2'-deoxyadenosine (CdA) is a new antimetabolite with very promising effect in the treatment of chronic lymphoproliferative diseases. It has also been shown to have good activity in acute myelogenous leukemia in children. CdA induces DNA single strand breaks and poly(ADP)-ribosylation, apoptosis and is cytotoxic to non-proliferating as well as proliferating cells. Earlier, CdA has only been given as continuous infusion. Recently, however, pharmacokinetic studies have shown that the bioavailability of oral CdA is 50% and of s.c. injection 100%. Furthermore, studies of the intracellular pharmacokinetics shows that there is a prolonged retention of its nucleotide metabolites supporting intermittent dosing.