2. Academic Validation
  3. Pharmacokinetics of enzalutamide, an anti-prostate cancer drug, in rats

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

  • Arch Pharm Res. 2015 Nov;38(11):2076-82. doi: 10.1007/s12272-015-0592-9.
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 6,  Tae-Sung Koo 7
Affiliations

Affiliations

  • 1 Graduate School of New Drug Discovery and Development, Chungnam National University, Daejeon, Korea.
  • 2 Life Science Research Institute, Daewoong Pharmaceutical Corporation, Yongin, Korea.
  • 3 Center for Drug Discovery Technology, Korea Research Institute of Chemical Technology, Daejeon, Korea.
  • 4 Department of Medicinal Chemistry & Pharmacology, Korea University of Science and Technology, Daejeon, Korea.
  • 5 College of Pharmacy, Kangwon National University, Chuncheon, Korea.
  • 6 Graduate School of New Drug Discovery and Development, Chungnam National University, Daejeon, Korea. sungsub@cnu.ac.kr.
  • 7 Graduate School of New Drug Discovery and Development, Chungnam National University, Daejeon, Korea. kootae@cnu.ac.kr.
PMID: 25956695 DOI: 10.1007/s12272-015-0592-9
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; Excretion; Metabolsim; Pharmacokinetics; Tissue distribution.

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