Drug Res (Stuttg) 2013; 63(02): 84-89
DOI: 10.1055/s-0032-1333226
Original Article
© Georg Thieme Verlag KG Stuttgart · New York

Absorption, Distribution and Excretion of Radioactivity by Male Rats after a Single Intravenous or Subcutaneous Dose of 14C-azacitidine

T. Ichikawa
1   Discovery Research Laboratories, Nippon Shinyaku Co., Ltd, Kyoto, Japan
Y. Suda
1   Discovery Research Laboratories, Nippon Shinyaku Co., Ltd, Kyoto, Japan
T. Nakagawa
1   Discovery Research Laboratories, Nippon Shinyaku Co., Ltd, Kyoto, Japan
K. Nonaka
1   Discovery Research Laboratories, Nippon Shinyaku Co., Ltd, Kyoto, Japan
A. Nakamura
2   Clinical Pharmacology Division, Nippon Shinyaku Co., Ltd, Kyoto, Japan
S. Ochi
1   Discovery Research Laboratories, Nippon Shinyaku Co., Ltd, Kyoto, Japan
› Author Affiliations
Further Information

Publication History

received 20 February 2012

accepted 11 December 2012

Publication Date:
24 January 2013 (online)


The absorption, distribution and excretion of radioactivity were investigated in male Sprague-Dawley rats after a single intravenous or subcutaneous dose of 14C-azacitidine. After subcutaneous administration, 14C-azacitidine was rapidly absorbed and the radioactivity was distributed to the tissues. The absorption of radioactivity after subcutaneous administration was 76.6% of that observed after intravenous administration. There were no marked differences in the tissue distribution of the radioactivity between administration routes. The concentrations of radioactivity in most tissues, including the spleen and bone marrow, which are sites of action of azacitidine, were higher than those in the plasma. Particularly high concentrations of radioactivity were detected in the spleen, kidney and liver. The accumulation of radioactivity in blood cells increased from 0.5 to 48 h. The binding of azacitidine to serum protein was low at <9%, and the cumulative urinary and fecal excretion of radioactivity for 168 h after intravenous or subcutaneous administration was >95% of the administered dose, indicating that radioactivity did not accumulate in the tissues. The radioactivity was mainly excreted in the urine.

  • References

  • 1 Silverman LR, Mufti GJ. Methylation inhibitor therapy in the treatment of myelodysplastic syndrome. Nat Clin Pract Oncol 2005; 2: S12-S23
  • 2 Wolfer Jr GK, Rippon WB. Protocols for use of ultrafiltration in determination of free ligand concentration and of complexity of ligand/protein interactions. Clin Chem 1987; 33: 115-117
  • 3 Chan KK, Giannini DD, Staroscik JA et al. 5-Azacitidine hydrolysis kinetics measured by high-pressure liquid chromatography and 13C-NMR spectroscopy. J Pharm Sci 1979; 68: 807-812
  • 4 Zhao M, Rudek MA, He P et al. Quantification of 5-azacytidine in plasma by electrospray tandem mass spectrometry coupled with high-performance liquid chromatography. J Chromatogr B Analyt Technol Biomed Life Sci 2004; 813: 81-88
  • 5 Zhang J, Visser F, King KM et al. The role of nucleoside transporters in cancer chemotherapy with nucleoside drugs. Cancer Metastasis Rev 2007; 26: 85-110
  • 6 Tong Z, Damaraju V, Yao S et al. The role of human nucleoside transporters in uptake of 5-azacitidine, 5-aza-2'-deoxycytidine and gemcitabine. Poster presented at: 52nd American Society of Hematology Annual Meeting and Exposition; 2010 Dec 4–7; Orlando, FL
  • 7 Rius M, Stresemann C, Keller D et al. Human concentrative nucleoside transporter 1-mediated uptake of 5-azacytidine enhances DNA demethylation. Mol Cancer Ther 2009; 8: 225-231
  • 8 Rius M, Keller D, Brom M et al. Vectorial transport of nucleoside analogs from the apical to the basolateral membrane in double-transfected cells expressing the human concentrative nucleoside transporter hCNT3 and the export pump ABCC4. Drug Metab Dispos 2010; 38: 1054-1063
  • 9 Ritzel MWL, Ng AML, Yao SYM et al. Molecular identification and characterization of novel human and mouse concentrative Na+-nucleoside cotransporter proteins (hCNT3 and mCNT3) broadly selective for purine and pyrimidine nucleosides (system cib). J Biol Chem 2001; 276: 2914-2927
  • 10 Baldwin SA, Beal PR, Yao SY et al. The equilibrative nucleoside transporter family, SLC29. Pflugers Arch 2004; 447: 735-743
  • 11 Troetel WM, Weiss AJ, Stambaugh JE et al. Absorption, distribution, and excretion of 5-azacytidine (NSC-102816) in man. Cancer Chemother Rep 1972; 56: 405-411
  • 12 Qiu X, Hother C, Ralfkiær UM et al. Equitoxic doses of 5-azacytidine and 5-aza-2’deoxycytidine induce diverse immediate and overlapping heritable changes in the transcriptome. PloS One 2010; 5: e12994