Absorption Rate

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

PBPK Modeling of Inter-individual Variability in the Pharmacokinetics of Environmental Chemicals

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 and Your Pay Stub

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

Discovery of Novel GSK-3 β Inhibitors with Potent In Vitro and In Vivo Activities and Excellent Brain Permeability Using Combined Ligand- and Structure-based Virtual Screening

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

What is a Half-life?

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

3D-QSAR Studies and Molecular Docking on [5-(4-amino-1H-benzoimidazol-2-yl)-furan-2-yl]-phosphonic Acid Derivatives as Fructose-1,6-biphophatase Inhibitors

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

Docking and 3D-QSAR study of Thiourea Analogs as Potent Inhibitors of Influenza Virus Neuraminidase

Surflex-Dock was applied to study interactions between 30 thiourea analogs and neuraminidase (NA). The docking results showed that hydrogen bonding and electrostatic interactions were highly correlated with the activities of neuraminidase inhibitors (NIs), followed by hydrophobic and steric factors. Moreover, there was a strong correlation between the predicted binding affinity (total score) and experimental pIC50 … Continued

Modeling Disease Progression in Acute Stroke Using Clinical Assessment Scales

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