Asparaginases
Asparaginases are cell cycle–specific and act during the
G1phase. They include:
·
asparaginase
·
pegaspargase.
Asparaginase is administered parenterally. It’s
considered 100% bioavailable when administered I.V. and about 50% bioavailable
when administered I.M.
After administration, asparaginase remains inside
the blood ves-sels, with minimal distribution elsewhere. The metabolism of
as-paraginase is unknown; only trace amounts appear in urine.
Asparaginase and pegaspargase capitalize on the
biochemical dif-ferences between normal cells and tumor cells.
Most normal cells can synthesize asparagine, but
some tumor cells depend on other sources of asparagine for survival.
Asparaginase and pegaspargase help to degrade asparagine to aspartic acid and
ammonia. Deprived of their supply of asparagine, the tumor cells die.
Asparaginase is used primarily in combination with
standard chemotherapy to induce remission in patients with acute lympho-cytic
leukemia.
Pegaspargase is used to treat acute lymphocytic
leukemia in pa-tients who are allergic to the native form of asparaginase.
Asparaginase drugs may interact with other
drugs. Asparaginase and pegaspargase may reduce the effectiveness of
methotrexate. Concurrent use of asparaginase with prednisone or vincristine
in-creases the risk of toxicity. (See Adverse
reactions to asparagi-nase drugs.)
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