title: Bioavailability of azacitidine subcutaneous versus intravenous in patients with the myelodysplastic syndromes.
abstract: The primary objectives of this study were to characterize the absolute bioavailability of azacitidine after subcutaneous (SC) administration and to compare the single-dose pharmacokinetics of azacitidine following SC and intravenous (IV) administration. Six patients with myelodysplastic syndromes were randomly assigned according to a crossover design to treatment A, consisting of azacitidine administered as a single 75-mg/m(2) SC dose, or treatment B, consisting of azacitidine administered as a single 75-mg/m(2) IV infusion dose over 10 minutes. A minimum of 7 days and a maximum of 28 days were permitted between treatments. The study demonstrated good bioavailability of a SC azacitidine dose compared to an IV infusion treatment. The exposure profiles following SC drug administration illustrate measurable azacitidine levels with bioavailability (AUC) values within 89% of those measured following IV administration (range, 70%-112%). The median IV half-life was 0.36 +/- 0.02 hours compared to 0.69 +/- 0.14 hours for SC administration. Regardless of the route of administration, a single dose of azacitidine, 75 mg/m(2), was generally well tolerated.
authors.affiliation: Ohio State University Medical Center, 4th Floor Starling Loving Hall, 320 West 10th Avenue, Columbus, OH 43210, USA.
authors.forename: Guido
authors.initials: G
authors.lastname: Marcucci
authors.forename: Lewis
authors.initials: L
authors.lastname: Silverman
authors.forename: Mark
authors.initials: M
authors.lastname: Eller
authors.forename: Linda
authors.initials: L
authors.lastname: Lintz
authors.forename: C L
authors.initials: CL
authors.lastname: Beach
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019540:Area Under Curve; D001374:Azacitidine / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001682:Biological Availability; D018592:Cross-Over Studies; D005260:Female; D006207:Half-Life; D006801:Humans; D007262:Infusions, Intravenous; D007279:Injections, Subcutaneous; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000188:drug therapy*
chemical_list: D000964:Antimetabolites, Antineoplastic; D001374:Azacitidine