The rate at which a drug enters the body after administration is called the absorption rate, and is represented by the symbol ka. This is probably one of the simplest pharmacokinetic (PK) parameters to explain and understand. Let’s consider the case of oral administration first, then we can discuss other routes of administration. A drug … Continued
Generic PBPK models, applicable to a large number of substances, coupled to parameter databases and QSAR modules, are now available for predictive modelling of inter-individual variability in the absorption, distribution, metabolism and excretion of environmental chemicals. When needed, Markov chain Monte Carlo methods and multilevel population models can be jointly used for a Bayesian calibration … Continued
Bioavailability is another primary pharmacokinetic parameter (like Clearance and Volume of Distribution) that describes the fraction of administered drug that reaches the systemic circulation. As a fraction, bioavailability can take any real value between 0 and 1 (e.g. 0.54). Sometimes this is reported as a percentage instead of a decimal (e.g. 54%). To explain this, … Continued
Dysregulation of glycogen synthase kinase (GSK-3β) is implicated in the pathophysiology of many diseases, including type-2 diabetes, stroke, Alzheimer’s, and others. A multistage virtual screening strategy designed so as to overcome known caveats arising from the considerable flexibility of GSK-3β yielded, from among compounds in our in-house database and two commercial databases, new GSK-3β inhibitors … Continued
One of the most incorrectly used but most often quoted parameters is half life. The symbol for half-life is t1/2. The reason for the multitude of errors with half-life is that in most cases, the assumptions required to use half-life correctly are rarely valid. And when the assumptions are false, the derived interpretations are also … Continued
Fructose-1,6-biphophatase has been regarded as a novel therapeutic target for the treatment of type 2 diabetes mellitus (T2DM). 3D-QSAR and docking studies were performed on a series of [5-(4-amino-1H-benzoimidazol-2-yl)-furan-2-yl]-phosphonic acid derivatives as fructose-1,6-biphophatase inhibitors. The CoMFA and CoMSIA models using thirty-seven molecules in the training set gave rcv2 values of 0.614 and 0.598, r2 values … Continued
This article demonstrates techniques for describing and predicting disease progression in acute stroke by modeling scores measured using clinical assessment scales, accommodating dropout as an additional source of information. Scores assessed using the National Institutes of Health Stroke Scale and the Barthel Index in acute stroke patients were used to model the time course of … Continued
Structure-based quantitative structure-activity relationship (QSAR) studies on a series of checkpoint kinase 1 (Chk1) inhibitors were performed to find the key structural features responsible for their inhibitory activity. Molecular docking was employed to explore the binding mode of all inhibitors at the active site of Chk1 and determine the active conformation for the QSAR studies. … Continued
3D-QSAR and docking studies were performed on a series of pyrazolo[4,3-h]quinazoline-3-carboxamides as CDK2/CyA inhibitors. The CoMFA and CoMSIA models using 54 molecules in the training set, gave rcv2 values of 0.644 and 0.507, r2 values of 0.959 and 0.951, respectively.
