Absorption-distribution-metabolism-elimination and toxicology

ADMET In vitro absorption, distribution, metabolism, elimination, and toxicology. 

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. 

The general application of epidemiologic methods to developmental toxicity is described below and followed by a discussion of laboratory studies in rodents and rabbits. The bulk of data available in developmental toxicology are based on these protocols. Since the difference in human and animal response appears to rest in large part on differences in behavior, physiologic parameters, and xenobiotic absorption, distribution, metabolic fate, and elimination, a brief description of transplacental pharmacokinetics is also provided. 

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... 

There are limited data on the toxicokinetics of gasoline in humans and animals. Information on the toxicokinetics of several components of gasoline is available (see the ATSDR toxicological profiles for benzene, toluene, and xylene [ATSDR 1991, 1989, 1990]) it should be noted, however, that the interaction of these compounds may influence their individual absorption, distribution, metabolism, and elimination characteristics. 

It should be noted that the development of nanomedicine was not without challenge nanobased products present a variety of safety issues, including their absorption, distribution, metabolism and elimination, which may differ from those of pharmaceuticals. In addition, biomedical nanoscale materials are at present neither well characterized nor standardized, and their interactions with traditional drugs/devices/metaboHc pathways are largely unknown. The toxicological aspects of nanocopper materials should, therefore, always be borne in mind when developing new ideas or invasive devices. 

One critical limitation to improving the methods used in risk, assessments is the current database of toxicology studies, particularly the current prolocol(s) for metabolism and PK. studies. PK studies typically submitted to EPA-OPP for purposes of pesticide registration were designed to evaluate absorption, distribution in tissue.s and organs, metabolism, and elimination in fluids and excreta. The study protocols. 

Toxicology, Pharmacology and Metabolism. The dose-limiting toxicity of AMD473 in mice (and rats) is myelosuppression (leukopenia and thrombocytopenia). No renal-, liver- or neuro-toxicity has been observed [54]. Platinum pharmacokinetics following i.v. administration to mice (20 mg/kg) showed a biexponential decay in plasma with a rapid distribution (f1/2a °f 24 min) followed by a slow elimination (ti/2p of 44 h). Following oral dosing, platinum absorption was rapid (rmax of 0.5h) with a bioavailability of 40% [54]. Platinum accumulated mainly in the liver, kidney and spleen [54]. 

In vitro assays play a very important role in drug discovery. First, these assays provide a simple, convenient, and fast way to test the potency and drug properties of chemical entities to help advance them rapidly. The drug-like properties commonly refer to respectable absorption, adequate distribution, low metabolism, and complete elimination (ADME) from body and minimal toxicological risk. Second, the amount of compound available is often limited in the early drug discovery stage and it is not always feasible for preclinical animal studies. Thus, in vitro assays could be a more rapid alternative to screen compounds. Third, in vitro assays are also designed to answer specific... 

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