Absorption, metabolism, excretion and

Using the tools of molecular biology and genetics, research should define the mechanisms by which genes influence nutrient (L-tryptophan) absorption, metabolism, excretion, and other actions and also the mechanisms by which the nutrient (L-tryptophan) influences gene expression. Such studies should be productive and will clarify whether and how L-tryptophan may be primarily or secondarily involved in and during the pathogenesis of a variety of important chronic diseases. 

K Mizojiri, H Okabe, K Sugeno, A Misaki, M Ito, G Kominami, Y Esumi, M Takaichi, T Harada, H Seki, A Inaba. Studies on the metabolism and disposition of the new retinoid 4-[(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)carbamoyl] benzoic acid. 4th communication absorption, metabolism, excretion and plasma protein binding in various animals and man. Arzneimittelforschung 47 259-269, 1997. 

Historically, drug absorption, distribution, metabolism, excretion, and toxicity ADMET) studies in animal models were performed after the identification of a lead compound. In order to avoid costs, nowadays pharmaceutical companies evaluate the ADMET profiles of potential leads at an earlier stage of the development... 

Ekins S, Nikolsky Y, Nikolskaya T. Techniques application of systems biology to absorption, distribution, metabolism, excretion and toxicity. Trends Pharmacol Sci 2005 Apr 26(4) 202-9. 

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

Absorption, Distribution, Metabolism, Excretion and Toxicity (ADMET)... 

Repeating for emphasis - not aU poorly water-soluble compounds are equally solubilized by DMSO. The greaseball compounds will be much better solubilized than the brickdust compounds. The most common range of compound in DMSO stock concentrations in compound storage repositories is 2-20 mM. At conferences, organizations employing 2mM compound in DMSO stock solutions report fewer solubility problems. The downside is that the lower stock concentrations are more Hmited in utility in some absorption, distribution, metabolism, excretion and toxicity assays that require higher compound concentration. 

ADMET absorption, distribution, metabolism, excretion and toxicity BLW-ED block-localized wave function energy decomposition hERG human ether-a-go-go-related gene QSAR quantitative structure-activity relationship... 

The attraction of lipophilicity in medicinal chemistry is mainly due to Corwin Hansch s work and thus it is traditionally related to pharmacodynamic processes. However, following the evolution of the drug discovery process, lipophilicity is today one of the most relevant properties also in absorption, distribuhon, metabolism, excretion and toxicity (ADMET) prediction, and thus in drug profiling (details are given in Chapter 2). 

Hansch and Leo [13] described the impact of Hpophihdty on pharmacodynamic events in detailed chapters on QSAR studies of proteins and enzymes, of antitumor drugs, of central nervous system agents as well as microbial and pesticide QSAR studies. Furthermore, many reviews document the prime importance of log P as descriptors of absorption, distribution, metabolism, excretion and toxicity (ADMET) properties [5-18]. Increased lipophilicity was shown to correlate with poorer aqueous solubility, increased plasma protein binding, increased storage in tissues, and more rapid metabolism and elimination. Lipophilicity is also a highly important descriptor of blood-brain barrier (BBB) permeability [19, 20]. Last, but not least, lipophilicity plays a dominant role in toxicity prediction [21]. 

Abou-Donia MB, Nomeir AA, Bower JH, et al. 1990b. Absorption, distribution, excretion, and metabolism of a single oral dose of [14C] tri-ort/zo-cresyl phosphate (TOCP) in the male rat. Toxicology 65 61-74. 

Thus, %F is defined as the area under the curve normalized for administered dose. Blood drug concentration is affected by the dynamics of dissolution, solubility, absorption, metabolism, distribution, and elimination. In addition to %F, other pharmacokinetic parameters are derived from the drug concentration versus time plots. These include the terms to describe the compound s absorption, distribution, metabolism and excretion, but they are dependent to some degree on the route of administration of the drug. For instance, if the drug is administered by the intravenous route it will undergo rapid distribution into the tissues, including those tissues that are responsible for its elimination. 

Absorption maximum wavelengths, correlation equations for, 20 508t Absorption, metabolism, distribution, and excretion (ADME), predicting using diversity analysis, 6 18 Absorption properties, of sutures,... 

In the above-mentioned examples, the prediction of CYP-mediated compound interactions is a starting point in any metabolic pathway prediction or enzyme inactivation. This chapter presents an evolution of a standard method [1], widely used in pharmaceutical research in the early-ADMET (absorption, distribution, metabolism, excretion and toxicity) field, which provides information on the biotransformations produced by CYP-mediated substrate interactions. The methodology can be applied automatically to all the cytochromes whose 3 D structure can be modeled or is known, including plants as well as phase II enzymes. It can be used by chemists to detect molecular positions that should be protected to avoid metabolic degradation, or to check the suitability of a new scaffold or prodrug. The fully automated procedure is also a valuable new tool in early-ADMET where metabolite- or mechanism based inhibition (MBI) must be evaluated as early as possible. 

Among chemical-physics properties, lipophilicity is certainly a key parameter to understand and predict absorption, distribution, metabolism, excretion, and toxicity (ADMET) of NCE furthermore, it contributes to model ligand-target interactions underlying the pharmacodynamic phase [15],... 

Odani, T., Tanizawa, H., and Takino, Y. (1983a). Studies on the absorption, distribution, excretion and metabolism of ginseng saponins. 11. The absorption, distribution and excretion of ginsenoside Rgi in the rat. Chem. Pharm. Bull. 31, 292-298. 

In addition, bioinformatics databases have been expanded to integrate data on absorption, distribution, metabolism, excretion, and toxicity of drugs. Through these comprehensive sets of data, scientists have at their disposal powerful means to relate disease targets and their cellular functions to physiological and pathological processes. 

Takino Y, Odani T, Tanizawa FI, Flayashi T. (1982). Studies on the absorption, distribution, excretion, and metabolism of ginseng saponins I. Quantitative analysis of ginsenoside Rgl in rats. Chem Pharm Bull (Tokyo). 30(6) 2196-201. 

A number of recent success stories prove that DOS compounds provide invaluable tools for target validation — see Panel B of Fig. 4. The validation of the ADMET (absorption, distribution, metabolism, excretion, and toxicology) and in vivo properties of these compounds and their value as... 

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