Stein, Andrew (2017) Practical unidentifiability of receptor density in target mediated drug disposition models can lead to over-interpretation of drug concentration data. Practical unidentifiability of receptor density in target mediated drug disposition models can lead to over-interpretation of drug concentration data.

Abstract

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-parameterized given
the available data, resulting in the practical unidentifiability of
some of the model parameters, including the target receptor density.
In particular, when only PK data is available, the receptor density is almost always practically unidentifiable.
However, because practical identifiability is not regularly assessed,
incorrect interpretation of model fits to the data can be made. This
issue is illustrated using two case studies from the literature.

Item Type:	Article
Date Deposited:	13 Jun 2017 00:45
Last Modified:	13 Jun 2017 00:45
URI:	https://oak.novartis.com/id/eprint/31923