%0 Journal Article %A Stefan Zajic %A Stefaan Rossenu %A David Hreniuk %A Filippos Kesisoglou %A Jacqueline McCrea %A Fang Liu %A Li Sun %A Rose Witter %A Don Gauthier %A Roy Helmy %A Darrick Joss %A Tong Ni %A Randall Stoltz %A Julie Stone %A S. Aubrey Stoch %T The Absolute Bioavailability and Effect of Food on the Pharmacokinetics of Odanacatib: A Stable-Label i.v./Oral Study in Healthy Postmenopausal Women %D 2016 %R 10.1124/dmd.116.069906 %J Drug Metabolism and Disposition %P 1450-1458 %V 44 %N 9 %X A stable-label i.v./oral study design was conducted to investigate the pharmacokinetics (PK) of odanacatib. Healthy, postmenopausal women received oral doses of unlabeled odanacatib administered simultaneously with a reference of 1 mg i.v. stable 13C-labeled odanacatib. The absolute bioavailability of odanacatib was 30% at 50 mg (the phase 3 dose) and 70% at 10 mg, which is consistent with solubility-limited absorption. Odanacatib exposure (area under the curve from zero to infinity) increased by 15% and 63% when 50 mg was administered with low-fat and high-fat meals, respectively. This magnitude of the food effect is unlikely to be clinically important. The volume of distribution was ∼100 liters. The clearance was ∼0.8 l/h (13 ml/min), supporting that odanacatib is a low–extraction ratio drug. Population PK modeling indicated that 88% of individuals had completed absorption of >80% bioavailable drug within 24 hours, with modest additional absorption after 24 hours and periodic fluctuations in plasma concentrations contributing to late values for time to Cmax in some subjects. %U https://dmd.aspetjournals.org/content/dmd/44/9/1450.full.pdf