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Bioavailability of Azacitidine Subcutaneous Versus Intravenous in Patients With the Myelodysplastic Syndromes
Author(s) -
Marcucci Guido,
Silverman Lewis,
Eller Mark,
Lintz Linda,
Beach C. L.
Publication year - 2005
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/0091270004271947
Subject(s) - azacitidine , bioavailability , pharmacokinetics , medicine , crossover study , pharmacology , myelodysplastic syndromes , chemistry , bone marrow , biochemistry , gene expression , alternative medicine , pathology , dna methylation , gene , placebo
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.