title: The Absolute Bioavailability and Effect of Food on the Pharmacokinetics of Odanacatib: A Stable-Label i.v./Oral Study in Healthy Postmenopausal Women.
abstract: 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 (13)C-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.
authors.affiliation: Merck & Co., Inc., Kenilworth, New Jersey (S.Z., S.R., D.H., F.K., J.M., F.L., L.S., R.W., D.G., R.H., D.J., T.N., J.S., S.A.S.); and Covance Clinical Research Unit, Evansville, Indiana (R.S.) szajic@gmail.com.
authors.forename: Stefan
authors.initials: S
authors.lastname: Zajic
authors.affiliation: Merck & Co., Inc., Kenilworth, New Jersey (S.Z., S.R., D.H., F.K., J.M., F.L., L.S., R.W., D.G., R.H., D.J., T.N., J.S., S.A.S.); and Covance Clinical Research Unit, Evansville, Indiana (R.S.).
authors.forename: Stefaan
authors.initials: S
authors.lastname: Rossenu
authors.affiliation: Merck & Co., Inc., Kenilworth, New Jersey (S.Z., S.R., D.H., F.K., J.M., F.L., L.S., R.W., D.G., R.H., D.J., T.N., J.S., S.A.S.); and Covance Clinical Research Unit, Evansville, Indiana (R.S.).
authors.forename: David
authors.initials: D
authors.lastname: Hreniuk
authors.affiliation: Merck & Co., Inc., Kenilworth, New Jersey (S.Z., S.R., D.H., F.K., J.M., F.L., L.S., R.W., D.G., R.H., D.J., T.N., J.S., S.A.S.); and Covance Clinical Research Unit, Evansville, Indiana (R.S.).
authors.forename: Filippos
authors.initials: F
authors.lastname: Kesisoglou
authors.affiliation: Merck & Co., Inc., Kenilworth, New Jersey (S.Z., S.R., D.H., F.K., J.M., F.L., L.S., R.W., D.G., R.H., D.J., T.N., J.S., S.A.S.); and Covance Clinical Research Unit, Evansville, Indiana (R.S.).
authors.forename: Jacqueline
authors.initials: J
authors.lastname: McCrea
authors.affiliation: Merck & Co., Inc., Kenilworth, New Jersey (S.Z., S.R., D.H., F.K., J.M., F.L., L.S., R.W., D.G., R.H., D.J., T.N., J.S., S.A.S.); and Covance Clinical Research Unit, Evansville, Indiana (R.S.).
authors.forename: Fang
authors.initials: F
authors.lastname: Liu
authors.affiliation: Merck & Co., Inc., Kenilworth, New Jersey (S.Z., S.R., D.H., F.K., J.M., F.L., L.S., R.W., D.G., R.H., D.J., T.N., J.S., S.A.S.); and Covance Clinical Research Unit, Evansville, Indiana (R.S.).
authors.forename: Li
authors.initials: L
authors.lastname: Sun
authors.affiliation: Merck & Co., Inc., Kenilworth, New Jersey (S.Z., S.R., D.H., F.K., J.M., F.L., L.S., R.W., D.G., R.H., D.J., T.N., J.S., S.A.S.); and Covance Clinical Research Unit, Evansville, Indiana (R.S.).
authors.forename: Rose
authors.initials: R
authors.lastname: Witter
authors.affiliation: Merck & Co., Inc., Kenilworth, New Jersey (S.Z., S.R., D.H., F.K., J.M., F.L., L.S., R.W., D.G., R.H., D.J., T.N., J.S., S.A.S.); and Covance Clinical Research Unit, Evansville, Indiana (R.S.).
authors.forename: Don
authors.initials: D
authors.lastname: Gauthier
authors.affiliation: Merck & Co., Inc., Kenilworth, New Jersey (S.Z., S.R., D.H., F.K., J.M., F.L., L.S., R.W., D.G., R.H., D.J., T.N., J.S., S.A.S.); and Covance Clinical Research Unit, Evansville, Indiana (R.S.).
authors.forename: Roy
authors.initials: R
authors.lastname: Helmy
authors.affiliation: Merck & Co., Inc., Kenilworth, New Jersey (S.Z., S.R., D.H., F.K., J.M., F.L., L.S., R.W., D.G., R.H., D.J., T.N., J.S., S.A.S.); and Covance Clinical Research Unit, Evansville, Indiana (R.S.).
authors.forename: Darrick
authors.initials: D
authors.lastname: Joss
authors.affiliation: Merck & Co., Inc., Kenilworth, New Jersey (S.Z., S.R., D.H., F.K., J.M., F.L., L.S., R.W., D.G., R.H., D.J., T.N., J.S., S.A.S.); and Covance Clinical Research Unit, Evansville, Indiana (R.S.).
authors.forename: Tong
authors.initials: T
authors.lastname: Ni
authors.affiliation: Merck & Co., Inc., Kenilworth, New Jersey (S.Z., S.R., D.H., F.K., J.M., F.L., L.S., R.W., D.G., R.H., D.J., T.N., J.S., S.A.S.); and Covance Clinical Research Unit, Evansville, Indiana (R.S.).
authors.forename: Randall
authors.initials: R
authors.lastname: Stoltz
authors.affiliation: Merck & Co., Inc., Kenilworth, New Jersey (S.Z., S.R., D.H., F.K., J.M., F.L., L.S., R.W., D.G., R.H., D.J., T.N., J.S., S.A.S.); and Covance Clinical Research Unit, Evansville, Indiana (R.S.).
authors.forename: Julie
authors.initials: J
authors.lastname: Stone
authors.affiliation: Merck & Co., Inc., Kenilworth, New Jersey (S.Z., S.R., D.H., F.K., J.M., F.L., L.S., R.W., D.G., R.H., D.J., T.N., J.S., S.A.S.); and Covance Clinical Research Unit, Evansville, Indiana (R.S.).
authors.forename: S Aubrey
authors.initials: SA
authors.lastname: Stoch
mesh_terms: D000284:Administration, Oral; D000368:Aged; D019540:Area Under Curve; D001682:Biological Availability; D001713:Biphenyl Compounds / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D005260:Female; D018565:Food-Drug Interactions; D006207:Half-Life; D006801:Humans; D007262:Infusions, Intravenous; D008875:Middle Aged; D017698:Postmenopause
chemical_list: D001713:Biphenyl Compounds; C527128:odanacatib