Absorption-distribution-metabolism-elimination

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. 

ADMET absorption, distribution, metabolism, elimination and toxicity... 

ADME absorption/distribution/metabolism/elimination (excretion)... 

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. 

The basis for understanding the health benefits of isoflavones requires detailed knowledge on the absorption, distribution, metabolism, elimination, and bioavailability of these phytoestrogens that demands robust, precise, accurate, and affordable analyses from biological and other matrices. 

One PBPK model for chromium has been published. The O Flaherty model (O Flaherty 1993a, 1996) simulates the absorption, distribution, metabolism, elimination, and excretion of chromium(III) and chromium(VI) compounds in the rat. Two kinetic models describing the distribution and clearance of chromium(III) compounds in humans are described at the end of this section. 

Tab8.2 Clinical ADMET (Absorption, Distribution, Metabolism, Elimination and Toxicity) characteristics of atenolol, betaxolol, celiprolol, and nebivolol. For details and reference sources, see the text. 

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. 

Pharmacokinetics Considers Absorption Distribution Metabolism Elimination A summary of relevant facts which may be incomplete, depending on the data available References 1—6 and Summaries of Product Characteristics (SPC)... 

Individual processes Absorption. Distribution, Metabolism, Elimination... 

Absorption, distribution, metabolism, elimination 5 -adenylyl /1-y-imidodiphosphate Aminohexanoic acid Adenosine monophosphate Apolipoprotein D... 

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