| Indication |
For the treatment of hairy cell leukaemia refractory to alpha interferon. |
| Mechanism of action |
Pentostatin is a potent transition state inhibitor of adenosine deaminase (ADA), the greatest activity of which is found in cells of the lymphoid system. T-cells have higher ADA activity than B-cells, and T-cell malignancies have higher activity than B-cell malignancies. The cytotoxicity that results from prevention of catabolism of adenosine or deoxyadenosine is thought to be due to elevated intracellular levels of dATP, which can block DNA synthesis through inhibition of ribonucleotide reductase. 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). |
| Absorption |
Not absorbed orally, crosses blood brain barrier. |
| Protein binding |
4% |
| Biotransformation |
Primarily hepatic, but only small amounts are metabolized. |
| Route of 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. |
| Toxicity |
LD50=128 mg/kg (mouse), side effects include lethargy, rash, fatigue, nausea and myelosuppression. |
| Affected organisms |
|