ADME absorption, disposition

D-MEDNEs Three-dimensional Markovian electron delocalization negentropies 3D-QSAR Three-dimensional quantitative structure activity relationship ADME Allied toxicological physicochemical and absorption Disposition... 

An understanding of the role of toxicokinetics and toxicodynamics in the manifestation of hazard is fundamental to designing safer chemicals and can guide early design choices. Toxicokinetics and toxicodynamics use the same principles to study toxicological phenomena as those that are used to study the therapeutic use of chemicals as medicines. Toxicokinetics is concerned with the time course of action of chemicals that involves the disposition of a chemical affected by absorption, distribution, metabohsm and excretion commonly referred to by the acronym ADME. 

The introduction and use of primary cells for ADMET assays may make a valuable contribution to the level and quality of information obtained from the tests. Absorption, distribution, metabolism, and excretion (ADME) encompass the disposition of a pharmaceutical compound within an organism. These four criteria influence the levels and kinetics of drug exposure to tissues and hence influence the performance and pharmacological activity of a compound as a drug. 

The fundamental principle of toxicology is the concept that the sixteenth century physician Paracelsus articulated in the 1500s sola dosis facit venenum or the dose makes the poison . The modem version of this observation is the dose-response relationship, which is experimentally and theoretically supported through pharmacokinetic and pharmacodynamic experimentation. Pharmacokinetics is concerned with the study of the time course of the disposition of drugs, specifically absorption, distribution, metabolism and elimination, often referred to as ADME. In non-technical terms it can be thought of as what the body does to the chemical. An understanding of the pharmacokinetic (in the case of dmgs) or toxicokinetic (all chemicals) profile is critical to estimate the... 

The clinical severity of statin-induced muscle toxicity is clearly influenced by variability in enzymes modulating statin disposition (absorption, distribution, metabolism, and elimination, ADME) (Fig. 1) [40], While many statins undergo phase I oxidation (atorvastatin, fluvastatin, lovastatin, simvastatin), the impact of phase I oxidation on others (pitavastatin, pravastatin, rosuvastatin) is very limited [41],... 

Drug metabolism or ADME evaluations determine absorption (how a compound gets into the body), distribution (where the compound goes), disposition (how long the compound stays), metabolism (whether the compound is changed and to what), and elimination (how the compound is removed or cleared) the fate of a compound in the body. 

The disposition of xenobiotics can be considered to occur in four interrelated phases (i.e., absorption, distribution, metabolism, and excretion, collectively abbreviated as ADME). The major routes for the absorption of xenobiotics include skin, lungs (or gills), and the parenteral routes—intravenous (i.v.), intraperitoneal (i.p.), subcutaneous (s.c.), and intramuscular (i.m.). The commonest route for administration in toxicology studies is per oral (p.o.) administration, with absorption of the test compound via the gastrointestinal (GI) tract the per-oral route is also the commonest route for exposure to a wide variety of environmental xenobiotics by fluid or food intake. 

Understanding the disposition of chemicals in organisms and how the body deals with a chemical once exposure has occurred should be described using the principles of toxicokinetics and toxicodynamics. The former includes the study of the time course of the disposition primarily of xenobiotics and examines the role of absorption, distribution, metabolism, and excretion (ADME) on toxicity. Each one of these components can be influenced through structural changes. Toxicodynamics includes the rate of absorption and excretion. This time-dependent phenomenon represents how fast certain chemicals can enter and leave the human system. Pesticides create problems to human and animals because they persist and remain in the body after ingestion. Pesticides are also time-dependent phenomena and represent how fast certain chemicals can enter and leave the human system. 

The kidney is a complex and cmcial excretory organ that plays an important role in numerous regulatory processes that include fluid and electrolyte balance (i.e., ultrafiltration, reabsorption, and secretion), control of blood pressure and volume, acid-base balance, and removal of waste products. It also has a significant endocrine function (Stockham and Scott 2008) and plays an important role in dmg disposition, i.e., the absorption, distribution, metabolism, and excretion (ADME) of dmgs. 

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