DRUG NAME: Hydroxyurea

CLASSIFICATION: alkylating agent Special pediatric considerations are noted when applicable, otherwise adult provisions apply. MECHANISM OF ACTION: Hydroxyurea, a hydroxylated molecule of urea, interferes with the synthesis of DNA via several proposed mechanisms, with little or no effect on RNA or protein synthesis. Hydroxyurea inhibits the conversion of DNA bases by blocking ribonucleotide reductase, thereby preventing conversion of ribonucleotides to deoxyribonucleotides. Hydroxyurea also inhibits the incorporation of thymidine into DNA, and may directly damage DNA.2,3 Hydroxyurea is cell-cycle specific for the S phase and may hold cells in the G1 phase.3 Hydroxyurea may also stimulate production of fetal hemoglobin and may have antiviral effects.2 PHARMACOKINETICS: Oral Absorption>80%,4 peak levels in 1-4 h rapidly and widely distributed; concentrates in leukocytes and erythrocytes; found in ascitic fluid cross blood brain barrier? yes volume of distribution1 20 L/m2; approximating total body water Distribution plasma protein binding1 75-80% 50-60 % metabolized by liver,4 small amount degraded by urease in intestinal bacteria active metabolite(s) no information found Metabolism inactive metabolite(s) urea,2 acetohydroxamic acid3 nonlinear process; saturable hepatic metabolism and renal excretion urine2-5 25-80 % (50 % as unchanged drug, 30 % as urea) feces no information found terminal half life4 3-4