Drug Groups

approved; investigational

Description

A potent inhibitor of adenosine deaminase. The drug is effective in the treatment of many lymphoproliferative malignancies, particularly hairy-cell leukemia. It is also synergistic with some other antineoplastic agents and has immunosuppressive activity. [PubChem]

Indication

For the treatment of hairy cell leukaemia refractory to alpha interferon.

Pharmacology

Pentostatin is an antineoplastic anti-metabolite used in the treatment of several forms of leukemia including acute nonlymphocytic leukemia and hairy cell leukemia. Anti-metabolites masquerade as purine or pyrimidine - which become the building blocks of DNA. They prevent these substances becoming incorporated in to DNA during the "S" phase (of the cell cycle), stopping normal development and division. It is a 6-thiopurine analogue of the naturally occurring purine bases hypoxanthine and guanine. Intracellular activation results in incorporation into DNA as a false purine base. An additional cytotoxic effect is related to its incorporation into RNA. Cytotoxicity is cell cycle phase-specific (S-phase).

Toxicity

LD₅₀=128 mg/kg (mouse), side effects include lethargy, rash, fatigue, nausea and myelosuppression.

Affected Organisms

Biotransformation

Primarily hepatic, but only small amounts are metabolized.

Absorption

Not absorbed orally, crosses blood brain barrier.

Half Life

5.7 hours (with a range between 2.6 and 16 hrs)

Protein Binding

4%

Elimination

In man, following a single dose of 4 mg/m2 of pentostatin infused over 5 minutes, approximately 90% of the dose was excreted in the urine as unchanged pentostatin and/or metabolites as measured by adenosine deaminase inhibitory activity.

Clearance

* 68 mL/min/m2

References

External Links