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Archives of Pharmacal Research

, Volume 38, Issue 11, pp 2076–2082 | Cite as

Pharmacokinetics of enzalutamide, an anti-prostate cancer drug, in rats

  • Tae-Heon Kim
  • Jong-Woo Jeong
  • Ji-Hye Song
  • Kyeong-Ryoon Lee
  • Sunjoo Ahn
  • Sung-Hoon Ahn
  • Sungsub KimEmail author
  • Tae-Sung KooEmail author
Research Article

Abstract

We characterized the pharmacokinetics of enzalutamide, a novel anti-prostate cancer drug, in rats after intravenous and oral administration in the dose range 0.5–5 mg/kg. Tissue distribution, liver microsomal stability, and plasma protein binding were also examined. After intravenous injection, systemic clearance, volumes of distribution at steady state (Vss), and half-life (T½) remained unaltered as a function of dose, with values in the ranges of 80.4–86.3 mL/h/kg, 1020–1250 mL/kg, and 9.13–10.6 h, respectively. Following oral administration, absolute oral bioavailability was 89.7 % and not dose-dependent. The recoveries of enzalutamide in urine and feces were 0.0620 and 2.04 %, respectively. Enzalutamide was distributed primarily in 10 tissues (brain, liver, kidneys, testis, heart, spleen, lungs, gut, muscle, and adipose) and tissue-to-plasma ratios of enzalutamide ranged from 0.406 (brain) to 10.2 (adipose tissue). Further, enzalutamide was stable in rat liver microsomes, and its plasma protein binding was 94.7 %. In conclusion, enzalutamide showed dose-independent pharmacokinetics at intravenous and oral doses of 0.5–5 mg/kg. Enzalutamide distributed primarily to 10 tissues and appeared to be eliminated primarily by metabolism.

Keywords

Enzalutamide Pharmacokinetics Tissue distribution Metabolsim Excretion 

Notes

Acknowledgments

This work was supported by the research fund of Chungnam National University.

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Copyright information

© The Pharmaceutical Society of Korea 2015

Authors and Affiliations

  • Tae-Heon Kim
    • 1
  • Jong-Woo Jeong
    • 1
  • Ji-Hye Song
    • 1
  • Kyeong-Ryoon Lee
    • 2
  • Sunjoo Ahn
    • 3
    • 4
  • Sung-Hoon Ahn
    • 3
    • 5
  • Sungsub Kim
    • 1
    Email author
  • Tae-Sung Koo
    • 1
    Email author
  1. 1.Graduate School of New Drug Discovery and DevelopmentChungnam National UniversityDaejeonKorea
  2. 2.Life Science Research InstituteDaewoong Pharmaceutical CorporationYonginKorea
  3. 3.Center for Drug Discovery TechnologyKorea Research Institute of Chemical TechnologyDaejeonKorea
  4. 4.Department of Medicinal Chemistry & PharmacologyKorea University of Science and TechnologyDaejeonKorea
  5. 5.College of PharmacyKangwon National UniversityChuncheonKorea

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