Orteronel (TAK-700) is a novel and selective inhibitor of CYP17A1, which is 
expressed in testicular, adrenal and prostate tumor tissues. Orteronel is 
currently in Phase-III clinical development for metastatic castration-resistant 
prostate patients. The objective of the study is to assess the permeability, 
metabolic stability (in various preclinical and human liver microsomes), 
identify the major CYPs involved in the metabolism of Orteronel. We have also 
studied the pharmacokinetics and excretion of Orteronel in Sprague-Dawley rats. 
Orteronel was found to be stable in various liver microsomes tested. The 
half-life (t ½) of Orteronel with intravenous (i.v.) route was found to be 1.65 
± 0.22 h. The clearance and volume of distribution by i.v. route for Orteronel 
were found to be 27.5 ± 3.09 mL/min/kg and 3.94 ± 0.85 L/kg, respectively. The 
absorption of Orteronel was rapid, with maximum concentrations of drug in plasma 
of 614 ± 76.4, 1,764 ± 166, 4,652 ± 300 and 17,518 ± 3,178 ng/mL attained at 
0.38, 0.75, 0.50 and 0.83 h, respectively, after oral administration of 
Orteronel at 5, 10, 30 and 100 mg/kg as a suspension. In the dose proportional 
oral pharmacokinetic study, the mean t ½ by oral route was found to be ~3.5 h 
and bioavailability ranged between 69 and 89 %. The primary route of elimination 
for Orteronel is urine.