Purine analogues are incorporated into DNA and RNA, interfer-ing with nucleic acid synthesis and replication. They include:
· fludarabine phosphate
The pharmacokinetics of purine analogues aren’t clearly defined. They’re largely metabolized in the liver and excreted in urine.
As with the other antimetabolites, fludarabine, mercaptopurine, and thioguanine first must be converted via phosphorylation (in-troduction to a phosphate) to the nucleotide level to be active.
The resulting nucleotides are then incorporated into DNA, where they may inhibit DNA and RNA synthesis as well as other metabol-ic reactions necessary for proper cell growth. Cladribine responds in a similar fashion.
This conversion to nucleotides is the same process that pyrimi-dine analogues go through but, in this case, it’s purine nucleotides that are affected. Purine analogues are cell cycle–specific as well, exerting their effect during that same S phase.
Pentostatin inhibits adenosine deaminase (ADA), causing an in-crease in intracellular levels of deoxyadenosine triphosphate. This leads to cell damage and death. The greatest activity of ADA is in cells of the lymphoid system, especially malignant T cells.
Purine analogues are used to treat acute and chronic leukemias and may be useful in the treatment of lymphomas.
No significant interactions occur with cladribine or thioguanine.
§ Taking fludarabine with pentostatin may cause severe pulmo-nary toxicity, which can be fatal.
§ Taking pentostatin with allopurinol may increase the risk of rash.
§ Taking pentostatin with vidarabine may enhance the effect of vi-darabine and increase the risk of toxicity.
Concomitant administration of mercaptopurine and allopurinol may increase bone marrow suppression by decreasing mercapto-purine metabolism. (See Adverse reactions to purine analogues.)