ADMET, Absorption, distribution

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

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... 

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. 

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... 

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. 

All of the above information will prove invaluable in determining the potential methods for rational drug delivery. Particular attention should be paid to the relative hygroscopicity of the API, of course, any stability information, as well as the impurity profile and ADMET (absorption, distribution, metabolism, excretion, and toxicity) information. In short, the more information that is available when development activities are initiated, the easier it is to avoid common pitfalls and make development decisions more rationally. 

Fig. 1 The dual role of RNAi technology in drug development process. RNAi compounds are being extensively used as a drug target discovery and validation tool. At the same time, they hold the promise of being used as drugs themselves. HTS, high-throughput screening of small molecules ADMET, absorption, distribution, metabolism, excretion, toxicity studies.

ADMET Absorption, Distribution, Metabolism, Excretion, Toxicity... 

Some pharmacometricians may be involved in complex software projects, such as the development of software for ADMET (absorption, distribution, metabolism, excretion, and toxicity) predictions or software tools that can be used by other scientists. Examples of such tools include Perl-speaks-NONMEM (14) or Xpose (15). Such tasks often require a diverse set of programming skills and strong programming practices. 

ADMET Absorption distribution, metabolism, excretion, and toxicity APP Amyloid precursor protein... 

ADMET (Absorption, Distribution, Metabolism, Excretion and Toxicity) prediction has two separate, but coincident aims. Some assays, used in early preclinical development, are aimed at gaining insights into the likely performance of a compound in a later-stage preclinical assay. Ultimately, though, assays are aimed at gaining a strong indication of how a compound will react once it is in a human metabolic environment. 

Identification of additional predictive and simulation tools to leverage curated data, for example, ADMET (absorption, distribution, metabolism, elimination and toxicology). Rapid identification of privileged fragments that lead to selection of compounds of high interest for a specific target. 

Abbreviations. ADMET = absorption, distribution, metabolism, excretion, toxicology CYP = cytochrome P450 ELISA = enzyme-linked immunosorbent assay PD = pharmacodynamics PK = pharmacokinetics — = not applicable. 

---