title: Pharmacokinetics of enzalutamide, an anti-prostate cancer drug, in rats.
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.
authors.affiliation: Graduate School of New Drug Discovery and Development, Chungnam National University, Daejeon, Korea.
authors.forename: Tae-Heon
authors.initials: TH
authors.lastname: Kim
authors.affiliation: Graduate School of New Drug Discovery and Development, Chungnam National University, Daejeon, Korea.
authors.forename: Jong-Woo
authors.initials: JW
authors.lastname: Jeong
authors.affiliation: Graduate School of New Drug Discovery and Development, Chungnam National University, Daejeon, Korea.
authors.forename: Ji-Hye
authors.initials: JH
authors.lastname: Song
authors.affiliation: Life Science Research Institute, Daewoong Pharmaceutical Corporation, Yongin, Korea.
authors.forename: Kyeong-Ryoon
authors.initials: KR
authors.lastname: Lee
authors.affiliation: Center for Drug Discovery Technology, Korea Research Institute of Chemical Technology, Daejeon, Korea.|Department of Medicinal Chemistry & Pharmacology, Korea University of Science and Technology, Daejeon, Korea.
authors.forename: Sunjoo
authors.initials: S
authors.lastname: Ahn
authors.affiliation: Center for Drug Discovery Technology, Korea Research Institute of Chemical Technology, Daejeon, Korea.|College of Pharmacy, Kangwon National University, Chuncheon, Korea.
authors.forename: Sung-Hoon
authors.initials: SH
authors.lastname: Ahn
authors.affiliation: Graduate School of New Drug Discovery and Development, Chungnam National University, Daejeon, Korea. sungsub@cnu.ac.kr.
authors.forename: Sungsub
authors.initials: S
authors.lastname: Kim
authors.affiliation: Graduate School of New Drug Discovery and Development, Chungnam National University, Daejeon, Korea. kootae@cnu.ac.kr.
authors.forename: Tae-Sung
authors.initials: TS
authors.lastname: Koo
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001549:Benzamides; D001682:Biological Availability; D004305:Dose-Response Relationship, Drug; D006207:Half-Life; D007275:Injections, Intravenous; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism*; D009570:Nitriles; D010669:Phenylthiohydantoin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D011471:Prostatic Neoplasms / Q000188:drug therapy; D011485:Protein Binding; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D009570:Nitriles; D010669:Phenylthiohydantoin; C540278:enzalutamide
keywords: Enzalutamide; Excretion; Metabolsim; Pharmacokinetics; Tissue distribution