ADME absorption, distribution metabolism, elimination

ADME Absorption, distribution, metabolism, elimination (excretion)... 

Medicinal chemists always followed and still apply the principle of chemical and biological similarity. Whenever they discover an active lead, they modify its chemical structure more or less systematically, to find similar analogs with improved activities, selectivities, ADME (absorption, distribution, metabolism, elimination) properties fewer side effects and less toxic properties. However, as discussed above, structurally closely related analogs may have significantly different specificity or even a completely different mode of action. 

As described previously, virtual screening and in silico design will accelerate the discovery of active lead compounds with new chemical scaffolds. The in silico prediction of physicochemical and ADME (absorption distribution metabolism elimination) properties, however, also are very critical for lead development. Actually, pharmacokinetics and toxicity have been identified as important causes of costly late-stage failures in drug development. The recently developed in silico approaches will increase model productivity in fine-tuned lead optimization to improve compound design and lead optimization. 

Lack of favorable ADME properties (absorption, distribution, metabolism, elimination) can preclude therapeutic use of an otherwise active molecule. The clinical pharmacokinetic parameters of clearance, half-life, volume of distribution, and bioavailability can be used to characterize ADME properties. 

In the following section, the calculation of the VolSurf parameters from GRID interaction energies will be explained and the physico-chemical relevance of these novel descriptors demonstrated by correlation with measured absorption/ distribution/metabolism/elimination (ADME) properties. The applications will be shown by correlating 3D molecular structures with Caco-2 cell permeabilities, thermodynamic solubilities and metabolic stabilities. Special emphasis will be placed on interpretation of the models by multivariate statistics, because a rational design to improve molecular properties is critically dependent on an understanding of how molecular features influence physico-chemical and ADME properties. 

The drug discovery and development processes are time consuming and costly endeavors. It has been reported that on average it takes 10 to 15 years and costs more than 800 million to bring a molecule from discovery to market.12 Compounds fail for various reasons. One that accounts for a reported 40% of failures in clinical trials is poor pharmacokinetics.3 In an effort to improve the number of compounds that exhibit optimal absorption, distribution, metabolism, elimination (ADME), and pharmacokinetic (PK) properties and reach development, drug metabolism and pharmacokinetic scientists continually implement new technologies and compound screening approaches. 

Another type of study is described by the term ADME (absorption, distribution, metabolism, and elimination). The rate of absorption describes how fast the drug substance enters the bloodstream and is a measure of bioavailability. The distribution in the body is measured to confirm that the substance reaches the target organ and that it does not accumulate in other organs. Metabolism is the chemical conversion of the substance in the body to other compounds and elimination describes how fast and by which route the substance and its metabolites are eliminated from the body. 

ADME—absorption, distribution, metabolism, and elimination. These are the defining pharmacokinetic characteristics of how a drug is handled by the body. 

When a person is alive, blood is continually pumped through and around the body by the heart when a drug is administered, it will be absorbed into the bloodstream (the route by which this occurs ultimately depends upon the route of administration). The body processes this drug through a process known as ADME (absorption, distribution, metabolism, and elimination). 

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