Relacatib (1-2 mg/kg 0.5 h intravenous infusion; 2-4 mg/kg oral bolus gavage) exhibits T1/2, CL or Vdss with 109 mins, 19.5 mL/min/kg, or 1.86 L/kg in male Sprague-Dawley rats and 168 mins, 11.7 mL/min/kg, and 1.79 L/kg in monkeys, respectively in a PK iv/po crossover studies. The oral bioavailability of Relacatib is 28% in the monkey and 89.4% in the rats[1].SB-462795 (subcutaneous injection; 12 mg/kg; blood sample is drawn 1.5, 4, 24, 48, and 72 h post dose administration) significantly inhibits resorption as assessed by two markers of bone resorption,the N- (NTx) and C-telopeptides (CTx) of type I collagen measured in serum. SB-462795 does not exhibit difference of serum osteocalcin (a biomarker of osteoblast activity) between SB-462795 and vehicle treated animalsexcept for the 48 h time point where a significant reduction (42% lower than baseline vs. 18% lower than baseline with vehicle treatment)[2].
| Animal Model: | Cynomolgus monkey[2] |
| Dosage: | 12 mg/kg |
| Administration: | Subcutaneous injection; single dose; blood sample is drawn 1.5, 4, 24, 48, and 72 h post dose administration |
| Result: | Was sufficiently high to significantly suppress bone resorption from 1.5 to 72 h post dosing. |
