The disposition and pharmacokinetics in humans of 5-azacytidine administered intravenously as a bolus or by continuous infusion.
The disposition of 5-[4-14C]azacytidine, administered i.v. as a bolus or continuous infusion, was studied in cancer patients. After bolus, plasma 14C levels exhibited as multiphasic disappearance pattern; half-life (t1/2, beta phase) = 3.4 to 6.2 hr. Of 14C in plasma, less than 2% was associated with 5-[4-14C]azacytidine 30 min after dose. The ratios of 14C levels were: red cells/plasma, approximately 0.8; leukocytes/plasma, 1.1 to 2.3; nucleic acids/leukocytes, 0.2 to 0.43; sputum/plasma, 0.05 to 0.17. Urinary excretion (3 days) accounted for 73 to 98% of 14C, LEss than 1% in feces. The relative concentration of 5-azacytidine in plasma with continuous infusion stayed higher than with bolus; urinary excretion was similar. Fewer side effects were observed with continuous infusion than with bolus. The stability of 5-azacytidine was determined in various media at several temperatures by thin layer chromatography and nuclear magnetic resonance. At 20 degrees in Ringer's lactate (pH 6.2), the t1/2 was 94 to 100 hr. Stability increased with lowering of temperature and pH. From our data we conclude that 5-azacytidine should be given by continuous infusion rather than as a bolus.
D001374:Azacitidine / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism* / Q000627:therapeutic use; D002855:Chromatography, Thin Layer; D004912:Erythrocytes / Q000378:metabolism; D005243:Feces / Q000032:analysis; D006801:Humans; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007263:Infusions, Parenteral; D007275:Injections, Intravenous; D007938:Leukemia / Q000188:drug therapy; D007962:Leukocytes / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D009362:Neoplasm Metastasis / Q000188:drug therapy; D009696:Nucleic Acids / Q000032:analysis; D012709:Serum Albumin / Q000032:analysis; D012997:Solvents; D013183:Sputum / Q000032:analysis; D013696:Temperature; D013997:Time Factors; D014508:Urea / Q000652:urine
D009696:Nucleic Acids; D012709:Serum Albumin; D012997:Solvents; D014508:Urea; D001374:Azacitidine