Marcucci Guido, Silverman Lewis, Eller Mark, Lintz Linda, Beach C L
Ohio State University Medical Center, 4th Floor Starling Loving Hall, 320 West 10th Avenue, Columbus, OH 43210, USA.
J Clin Pharmacol. 2005 May;45(5):597-602. doi: 10.1177/0091270004271947.
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.
本研究的主要目的是表征阿扎胞苷皮下注射后的绝对生物利用度，并比较阿扎胞苷皮下注射和静脉注射后的单剂量药代动力学。6例骨髓增生异常综合征患者根据交叉设计随机分配至治疗A组，接受75mg/m²阿扎胞苷单次皮下注射剂量治疗；或治疗B组，接受75mg/m²阿扎胞苷在10分钟内单次静脉输注剂量治疗。两次治疗之间允许间隔至少7天且最长28天。该研究表明，与静脉输注治疗相比，皮下注射阿扎胞苷剂量具有良好的生物利用度。皮下给药后的暴露曲线显示，阿扎胞苷水平可测，其生物利用度（AUC）值在静脉给药后测量值的89%以内（范围为70%-112%）。静脉注射的中位半衰期为0.36±0.02小时，皮下注射为0.69±0.14小时。无论给药途径如何，75mg/m²的单剂量阿扎胞苷通常耐受性良好。
