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.