The Human Pharmacokinetics of Odanacatib, a Novel Cathepsin K Inhibitor, Predicted by Interspecies Scaling: a Retrospective Analysis

Abstract

Aim: The objective of this exercise was to explore the utility of allometry for predicting intravenous and oral pharmacokinetics of odanacatib. Methods: The relation between the pharmacokinetic parameters (viz., volume of distribution and clearance [CL]) and body weight was examined across four species, using double logarithmic plots to predict volume of distribution and CL using simple allometry and biliary correction factors. Results: Best concurrence of intravenous plasma exposure of odanacatib in humans was obtained with the values predicted from CL value using CF2 (bile flow rate/body weight) correction factor. Conclusion: The outcome of this exercise indicates that interspecies scaling with suitable correction factors could be used to predict the human pharmacokinetics of odanacatib.

Prediction of Human Pharmacokinetics of Bendamustine from Preclinical Species Pharmacokinetics Based on Normalizing Time Course Profiles

“…In addition, to scientific challenges and optimization of the experimental designs for better allometry predictions, Srinivas (2010) has provided insights on how to effectively use allometry for clinical candidate selection and answer some early drug development questions [15]. Previously, we have used these concepts in the prediction of pharmacokinetic parameters across diverse compounds representing various therapeutic areas [16][17][18][19][20][21][22][23].…”