Pharmacokinetics, distribution and excretion of YM155 monobromide, a novel small‐molecule survivin suppressant, in male and pregnant or lactating female rats

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.