Physiologically based pharmacokinetic (PBPK) models are composed of a series of differential equations and have been implemented in a number of commercial software packages. These models require species-specific and compound-specific input parameters and allow for the prediction of plasma and tissue concentration time profiles after intravenous and oral administration of compounds to animals and humans. PBPK models allow the early integration of a wide variety of preclinical data into a mechanistic quantitative framework. Use of PBPK models allows the experimenter to gain insights into the properties of a compound, helps to guide experimental efforts at the early stages of drug discovery, and enables the prediction of human plasma concentration time profiles with minimal (and in some cases no) animal data. In this review, the application and limitations of PBPK techniques in drug discovery are discussed. Specific reference is made to its utility (1) at the lead development stage for the prioritization of compounds for animal PK studies and (2) at the clinical candidate selection and "first in human" stages for the prediction of human PK.
Reports an error in "A theory of the discovery and predication of relational concepts" by Leonidas A. A. Doumas, John E. Hummel and Catherine M. Sandhofer (Psychological Review, 2008[Jan], Vol 115, 1-43). In Figure 4, the RB unit (rectangle) labeled "causer gravity" should be conn...
We establish a correspondence between the electric dipole matrix elements of
A polyatomic symmetric top molecule in a precessing state and the magnetic
Dipole matrix elements of a magnetic dipole associated with an elemental spin
$F$. It is shown that this correspondence makes it possible to perform...
We present a new parallel implementation of the PINpointing Orbit
Crossing-Collapsed HIerarchical Objects (PINOCCHIO) algorithm, a quick tool,
Based on Lagrangian Perturbation Theory, for the hierarchical build-up of Dark
Matter halos in cosmological volumes. To assess its ability to predict halo
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