A Priori Identifiability of Target-Mediated Drug Disposition Models and Approximations

A Tutorial on Target-Mediated Drug Disposition (TMDD) Models

Target-mediated drug disposition (TMDD) is the phenomenon in which a drug binds with high affinity to its pharmacological target site (such as a receptor) to such an extent that this affects its pharmacokinetic characteristics.1 The aim of this Tutorial is to provide an introductory guide to the mathematical aspects of TMDD models for pharmaceutical researchers. Examples of Berkeley Madonna2 co...

Practical unidentifiability of receptor density in target mediated drug disposition models can lead to over-interpretation of drug concentration data

For monoclonal antibodies, mathematical models of target mediated drug disposition (TMDD) are often fit to data in order to estimate key physiological parameters of the system. These parameter estimates can then be used to support drug development by assisting with the assessment of whether the target is druggable and what the first in human dose should be. The TMDD model is almost always over-...

A mathematical analysis of rebound in a target-mediated drug disposition model: I.without feedback.

We consider the possibility of free receptor (antigen/cytokine) levels rebounding to higher than the baseline level after one or more applications of an antibody drug using a target-mediated drug disposition model. Using geometry and dynamical systems analysis, we show that rebound will occur if and only if the elimination rate of the drug-receptor product is slower than the elimination rates o...

TITLE : Application of Target - Mediated Drug Disposition Model to Small Molecule Heat Shock Protein 90 Inhibitors

Exponential Models: Approximations for Probabilities

Welch & Peers (1963) used a root-information prior to obtain posterior probabilities for a scalar parameter exponential model and showed that these Bayes probabilities had the confidence property to second order asymptotically. An important undercurrent of this indicates that the constant information reparameterization provides location model structure, for which the confidence property ...