ADMET Drug distribution Excretion

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.

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... 

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]. 

More recently the concept of ADMET profile (Absorption Distribution Metabolism Excretion Toxicity profile) has further streamlined the molecular pharmacology aspects of these drugs with the ultimate objective of providing efficient target directed drugs with least toxicity. 

Instead, due to the multi-objective nature of drug discovery, other factors, such as absorption, distribution, metabolism, excretion, toxicity (ADMET), selectivity and cost, molecular screening libraries need to be carefully planned and a number of design objectives must be taken into account (8). In recent times, MLD efforts have been exploring the use of multi-objective optimization (MOOP) techniques capable of designing libraries based on a number of properties simultaneously (9). 

II. Product Summaries Simulations Plus develops simulation and predictive modeling software for in silico compound screening and for preclinical and clinical drug development in the area of Absorption, Distribution, Metabolism, Excretion and Toxicity (ADMET). The available applications include GastroPlus, ADMET Predictor, ADMET Modeler, DDDPlus, and MembranePlus. 

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. 

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