Administration, distribution, metabolism, excretion ADME

The most important requirement that has to be met before Tc-radiopharmaceuticals can be used routinely in Nuclear Medicine is to have a registration file approved. For all radiopharmaceuticals, extensive information on the active ingredient (=the Tc-compound) is to be provided, including data on the exact chemical structure, the analytical methods to proof its purity and identity, the method to produce it from the precursor kit, batch data, etc. Another very important aspect of the registration file is the ADME (administration, distribution, metabolism, excretion) part, where especially the metabolic fate of the... 

Up to this point, the detection Unfit and sensitivity comparisons of the different sources have focused primarily on compoimds that ionize efficiently with all the techniques. It is important to understand the coverage or scope of an ionization technique across the chemical space of general interest, particularly when confronted with unknown compounds, or compounds whose structures are known but whose ionization properties have not been tested, and there is no time to assess a variety of options. This situation occurs in many drug discovery laboratories measuring in vitro ADME properties (administration, distribution, metabolism, excretion) where many different chemical species need to be assayed quickly. The data used to generate the relative efficiency values within a source in Tables 1-3 were used to calculate the relative MRM efficiency between the three sources and are shown in Table 13.4. The MALDI data were acquired in the most practical fashion to obtain a quantitative measurement where only a small percentage of the sample spot was ablated with a single raster. The ESI and APCI data were obtained by flow injection analysis at 200 and lOOOpL/min, respectively. Electrospray is the most sensitive ion source in nearly all... 

An oral ADME (absorption, distribution, metabolism, excretion, following oral administration of the pesticide) study may also be of utility in refining the risk assessment. If a default value for dermal absorption of 100 % is applicable based on the physico-chemical properties of a substance and an appropriate oral ADME study is available, the results of this study may be used to refine the default value for dermal absorption. It is required that the oral absorption is determined at low dose levels in experimental animals, in order to obtain an accurate estimate of the oral absorption. Based on theoretical grounds and supported by a comparison of oral and dermal absorption data available for twelve pesticides, it is assumed that dermal absorption will not exceed oral absorption (Hakkert et al unpublished data). 

Furthermore, pharmacokinetic administration, distribution, metabolism and excretion (ADME) factors affect drug bioavailability, efficacy and safety, and, thus, are a vital consideration in the selection process of oral drug candidates in development pipelines. Since solubility, permeability, and the fraction of dose absorbed are fundamental BCS parameters that affect ADME, these BCS parameters should prove useful in drug discovery and development. In particular, the classification can used to make the development process more efficient.For example, in the case of a drug placed in BCS Class II where dissolution is the rate-limiting step to absorption, formulation principles such as polymorph selection, salt selection, complex formation, and particle size reduction (i.e., nanoparticles) could be applied earlier in development to improve bioavailability. 

ADME (absorption, distribution, metabolism, excretion) trials. Animal species should be presented under each group by smallest (mouse) up to largest (monkey or other mammals). The route of administration should be presented under each species tested and the treatment group under each route of administration. For special toxicity trials, such as irritation and hemolysis trials, tabulate data as appropriate. An example of the format would be... 

Figure 41.6 Conceptual model of a druglike CORM. The number of CO ligands can be greater than 1 and the other ancillary ligands (L2-L6) can be the same or different. Distal substituents are just given as possible examples. ADME, administration, distribution, metabolism, and excretion PK, pharmacokinetics.

Absorption, distribution, metabolism and excretion (ADME) of the test substance after oral administration in one species, usually the rat, as well as dermal absorption in vitro (human and rat skin) or in vivo (rat)... 

Abbreviations. FDA, Food and Drug Administration IPEC, International Pharmaceutical Excipients Council ADME, adsorption, distribution, metabolism, and excretion. 

As was noted in Chapter 4, pharmacokinetic and pharmacodynamic effects are studied in nonclinical research. These topics are also of critical importance in clinical investigations. A drug s pharmacokinetics and pharmacodynamics are of considerable interest to clinicians who may prescribe the drug to patients once it is approved. Meaningful decisions about a drug s optimal use can only be made with an understanding of the time course of events that occur after the drug s administration, and both pharmacokinetics and pharmacodynamics are concerned with this time course. By consideration of the pharmacokinetic processes of absorption, distribution, metabolism, and excretion (ADME), the... 

Pharmacokinetics describe and predict the time-course of drug concentrations in body fluids. Pharmacokinetics answer the question what does the body do to the drug The following processes occur after administration of a drug absorption, distribution, metabolism, and excretion (ADME). PK models are quite common and well known in clinical drug development. In contrast to the PD models, the PK models can be clearly and easily classified into empirical and mechanistic models. In general, they are applied for the following situations ... 

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. 

If a lead molecule emerges from these additional studies on SAR, absorption, distribution, metabolism, and excretion (ADME) and toxicity, it acquires the clinical drug candidate status. After a short toxicological smdy it fulfills the criteria required for administration to humans for initial clinical studies. 

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