title: Absorption, Distribution, and Excretion of the Investigational Agent Orteronel (TAK-700) in Healthy Male Subjects: A Phase 1, Open-Label, Single-Dose Study.
abstract: This study evaluated the absorption, distribution, and excretion of orteronel, an investigational, nonsteroidal, reversible, selective 17,20-lyase inhibitor. Six healthy male subjects received a single 400-mg dose of radiolabeled [(14) C]-orteronel (18.5 kBq). The pharmacokinetics of [(14) C]-radioactivity, orteronel, and the primary metabolite M-I were characterized by ultra-performance liquid chromatography-tandem mass spectrometry, and mass balance recovery of [(14) C]-radioactivity was determined by liquid scintillation counting and accelerator mass spectrometry. Median time to maximum observed concentration of [(14) C]-radioactivity was 2.5 hours (plasma/whole blood) and of orteronel was 1 hour (plasma). Mean terminal half-life for [(14) C]-radioactivity in plasma and whole blood was 9.46 and 7.39 hours, respectively. For [(14) C]-radioactivity, the geometric mean whole blood-to-plasma ratios for maximum observed plasma/whole-blood concentration, area under the plasma concentration-time curve from time 0 to last quantifiable concentration (AUC0-last ), and AUC0-inf (AUC from time 0 to infinity) were 1.04, 0.92, and 0.93, respectively. Dose recovery accounted for 95.9% of the administered orteronel dose; the majority of excretion occurred by 96 hours postdose. The principal excretion route was via urine (mean, 77.5%; including 49.7% unchanged drug and 16.3% M-I) compared with 18.4% via feces. Three mild adverse events were reported; none were considered serious or related to orteronel.
authors.affiliation: Millennium Pharmaceuticals, Inc, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited, Cambridge, MA, USA.
authors.forename: Ajit
authors.initials: A
authors.lastname: Suri
authors.affiliation: Millennium Pharmaceuticals, Inc, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited, Cambridge, MA, USA.
authors.forename: Sandeepraj
authors.initials: S
authors.lastname: Pusalkar
authors.affiliation: Millennium Pharmaceuticals, Inc, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited, Cambridge, MA, USA.
authors.forename: Yuexian
authors.initials: Y
authors.lastname: Li
authors.affiliation: Millennium Pharmaceuticals, Inc, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited, Cambridge, MA, USA.
authors.forename: Shimoga
authors.initials: S
authors.lastname: Prakash
mesh_terms: D000328:Adult; D019540:Area Under Curve; D002853:Chromatography, Liquid; D065607:Cytochrome P-450 Enzyme Inhibitors / Q000009:adverse effects / Q000493:pharmacokinetics*; D006207:Half-Life; D006801:Humans; D007093:Imidazoles / Q000009:adverse effects / Q000493:pharmacokinetics*; D008297:Male; D009281:Naphthalenes / Q000009:adverse effects / Q000493:pharmacokinetics*; D013254:Steroid 17-alpha-Hydroxylase / Q000037:antagonists & inhibitors; D053719:Tandem Mass Spectrometry; D055815:Young Adult
chemical_list: D065607:Cytochrome P-450 Enzyme Inhibitors; D007093:Imidazoles; D009281:Naphthalenes; D013254:Steroid 17-alpha-Hydroxylase; C571806:orteronel
keywords: absorption; distribution; excretion; metastatic castration-resistant prostate cancer; orteronel