Premium
Pharmacokinetics, distribution and excretion of YM155 monobromide, a novel small‐molecule survivin suppressant, in male and pregnant or lactating female rats
Author(s) -
Minematsu Tsuyoshi,
Sonoda Takuya,
Hashimoto Tadashi,
Iwai Megumi,
Oppeneer Todd,
Felder Laurie,
Shirai Nobuaki,
Miyashita Aiji,
Usui Takashi
Publication year - 2012
Publication title -
biopharmaceutics and drug disposition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.419
H-Index - 58
eISSN - 1099-081X
pISSN - 0142-2782
DOI - 10.1002/bdd.1781
Subject(s) - pharmacokinetics , endocrinology , excretion , medicine , chemistry , urine
YM155 monobromide is a novel small‐molecule survivin suppressant. The pharmacokinetics, distribution and excretion of YM155/[ 14 C]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 [ 14 C]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. Copyright © 2012 John Wiley & Sons, Ltd.