Fig. 8
Unbound exposure corrected for cathepsin K potency vs. effect on biomarkers of bone resorption and cartilage degradation in various species. Circles represent bone resorption biomarkers (CTX-I and HP-1), while squares depict biomarkers of cartilage degradation (CTX-II). Rabbit biomarker data (open symbols) are from Week 7 and reflect % of vehicle control. Dog biomarker data (grey symbols) are from Day 28 and reflect % of baseline. Human biomarker data (black symbols) are from Day 7 and reflect % of baseline after 7-day dosing with 50, 100 and 200 mg MIV-711, respectively [30]. Potency corrected exposure data was calculated by taking the AUC0–24 h of MIV-711 and dividing by 24 h to reach Css (steady state concentration). Unbound Css was obtained by correcting for protein binding for the various species. Css was then divided by the Ki of MIV-711 for the various species