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Titlebook: Integration of Pharmacokinetics, Pharmacodynamics, and Toxicokinetics in Rational Drug Development; Avraham Yacobi (Director),Jerome P. Sk

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Assessment of Pharmacokinetic Drug Interactions in Clinical Drug Developmenthips of the chemical classes or metabolic pathways. A “Check-list” approach is often followed. More and more frequently, these studies serve several purposes including molecular modification to produce new compounds without the potential for interaction, and competitive marketing. One major issue, s
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Pharmacokinetics and Drug Metabolism in Animal Studies (ADME, Protein Binding, Mass Balance, Animal imal toxicity studies, and for the selection of the appropriate animal model for purposes of estimating a safe clinical dose. Examples of the usefulness of nonclinical pharmacokinetic data for explaining toxicity which occurred, while allowing clinical trials to continue, are presented.
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Use of Acute Toxicity Data in the Design and Interpretation of Subchronic and Chronic Toxicity Studiical for acute, subchronic and chronic dosing in the same species (rat). The importance and usefulness of careful considerations of toxicokinetic and toxicodynamic data obtained in acute experiments for the design of subchronic and chronic toxicity studies is discussed.
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Guidelines for Development of a New Diuretic Agentticular nephron site allows prediction of the degree of natriuresis that will occur and also the concomitant excretion of other electrolytes which may impact on adverse effects (e.g., potassium or magnesium).
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Preclinical Pharmacodynamics of Anti-Inflammatory Drugsnely for the evaluation of AI agents and includes some suggestions as to how one might approach the development of newer models that may help identify novel AI drugs with varying mechanisms of therapeutic action.
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Pharmacoepidemiology, Population Pharmacokinetics and New Drug Developmente events requiring at best a change in labeling; and at worst removal from the market at great cost, in terms of credibility and dollars, to both FDA and the pharmaceutical industry (FDA Drug Review, 1990).
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