Hydroxyurea

Hydroxyurea (Hydrea) inhibits the enzyme ribonu-cleotide reductase and thus depletes intracellular pools of deoxyribonucleotides, resulting in a specific impairment of DNA synthesis. The drug therefore is an S-phase specific agent whose action results in an accumulation of cells in the late G1- and early S-phases of the cell cycle.

Hydroxyurea is rapidly absorbed after oral administration, with peak plasma levels achieved approximately 1 to 2 hours after drug administration; its elimi nation half-life is 2 to 3 hours. The primary route of excretion is renal, with 30 to 40% of a dose excreted unchanged.

Hydroxyurea is used for the rapid lowering of blood granulocyte counts in patients with chronic granulocytic leukemia. The drug also can be used as maintenance therapy for patients with the disease who have become resistant to busulfan. Only a small percentage of patients with other malignancies have had even brief remissions induced by hydroxyurea administration.

Hematological toxicity, with white blood cells affected more than platelets, may occur. Megaloblastosis of the bone marrow also may be observed. Recovery is rapid, generally within 10 to 14 days after discontinuation of the drug. Some skin reactions, including hyper-pigmentation and hyperkeratosis, have been reported with chronic treatment.

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