title: Pharmacokinetics, distribution and excretion of YM155 monobromide, a novel small-molecule survivin suppressant, in male and pregnant or lactating female rats.
abstract: YM155 monobromide is a novel small-molecule survivin suppressant. The pharmacokinetics, distribution and excretion of YM155/[14C]YM155 were investigated using males and pregnant or lactating female rats after a single intravenous bolus administration. For the 0.1, 0.3 and 1 mg/kg YM155 doses given to male rats, increases in area under the plasma concentration-time curves were approximately proportional to the increase in the dose level. After administering [14C]YM155, radioactivity concentrations in the kidney and liver were highest among the tissues in both male and pregnant rats: e.g. 14.8- and 5.24-fold, respectively, and higher than in plasma at 0.1 h after dosing to male rats. The YM155 concentrations in the brain were lowest: 25-fold lower than in plasma. The transfer of radioactivity into fetuses was low (about 2-fold lower than in plasma). In lactating rats, the radioactivity was transferred into milk at a level 8- to 21-fold higher than for plasma. Radioactivity was primarily excreted in feces (64.0%) and urine (35.2%). The fecal excretion was considered to have occurred mainly by biliary excretion and partly by secretion across the gastrointestinal membrane from the blood to the lumen.
authors.affiliation: Drug Metabolism Research Laboratories, Astellas Pharma Inc., Osaka, Japan. tsuyoshi.minematsu@astellas.com
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Minematsu
authors.forename: Takuya
authors.initials: T
authors.lastname: Sonoda
authors.forename: Tadashi
authors.initials: T
authors.lastname: Hashimoto
authors.forename: Megumi
authors.initials: M
authors.lastname: Iwai
authors.forename: Todd
authors.initials: T
authors.lastname: Oppeneer
authors.forename: Laurie
authors.initials: L
authors.lastname: Felder
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Shirai
authors.forename: Aiji
authors.initials: A
authors.lastname: Miyashita
authors.forename: Takashi
authors.initials: T
authors.lastname: Usui
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D001646:Bile / Q000737:chemistry; D001798:Blood Proteins / Q000378:metabolism; D005243:Feces / Q000737:chemistry; D005260:Female; D007093:Imidazoles / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D007774:Lactation / Q000378:metabolism*; D008297:Male; D008431:Maternal-Fetal Exchange; D008869:Microtubule-Associated Proteins / Q000037:antagonists & inhibitors; D009285:Naphthoquinones / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D010920:Placenta / Q000378:metabolism; D011247:Pregnancy / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077022:Survivin; D014018:Tissue Distribution
chemical_list: D000970:Antineoplastic Agents; C516989:Birc5 protein, rat; D001798:Blood Proteins; D007093:Imidazoles; D008869:Microtubule-Associated Proteins; D009285:Naphthoquinones; D000077022:Survivin; C523798:sepantronium