Orteronel

In vitro, TAK-700 shows the potent inhibitory activity against rat and human steroid 17,20-lyase with IC50 of 54 nM and 38 nM, respectively. While other CYP isoforms including 11-hydroxylase and CYP3A4 are not significantly affected by TAK-700. ^[1] In microsomes expressing human CYP isoforms, TAK-700 exhibit greater inhibitory effects on 17,20-lyase with IC50 of 19 nM compared to the other CYP isoforms. ^[1] TAK-700 shows the inhibitory activity against monkey 17,20-lyase and 17-hydroxylase with IC50 of 27 nM and 38 nM, respectively. ^[2] In monkey adrenal cells, TAK-700 inhibits the ACTH stimulated production of DHEA and androstenedione with IC50 of 110 nM and 130 nM, respectively. Moreover, TAK-700 also potently inhibits DHEA production in human adrenocortical tumor line H295R cells with IC50 of 37 nM. ^[2]

In cynomolgus monkeys, oral treatment of TAK-700 at a dose of 1 mg/kg markedly reduces serum testosterone and dehydroepiandrosterone (DHEA) levels. ^[1] Oral treatment of TAK-700 at a dose of 1 mg/kg results in favorable pharmacokinetic parameters with T_max, C_max, t_1/2 and AUC_{0-24 hours} of 1.7 hours, 0.147 μg/mL, 3.8 hours and 0.727 μg h/mL, respectively. ^[2]

• Animal Models

  Adult male cynomolgus monkeys.

• Dosages

  ≤1 mg/kg

• Administration

  Administered via p.o.