Absorption, distribution, metabolism factors

The answer is e. (Hardman, p 21J The fraction of a drug dose absorbed after oral administration is affected by a wide variety of factors that can strongly influence the peak blood levels and the time to peak blood concentration. The Vd and the total body clearance (Vd x first-order fte) also are important in determining the amount of drug that reaches the target tissue. Only the area under the blood concentration-time curve, however, reflects absorption, distribution, metabolism, and excretion factors it is the most reliable and popular method of evaluating bioavailability... 

Uncertainty factors An uncertainty factor of 10 was retained for interspecies variability to account for possible variability in arsine-induced hemolysis and progression to renal effects. An uncertainty factor for intraspecies variability of 3 was used, because the hemolytic response is likely to occur to a similar extent and with similar susceptibility in most individuals. This was based on the consideration that physiologic parameters (e.g., absorption, distribution, metabolism, structure of... 

Nearly 15 years after Patched s speech, we still face the same problems that he highlighted. Medicinal chemists often synthesize a potent molecule and find later that it has poor exposure in vivo, and thus poor efficacy. Poor exposure can be caused by many different factors. Most of the factors affecting exposure are commonly known by acronym ADME - absorption, distribution, metabolism, and excretion. A fifth factor, solubility, is also very important and is commonly considered to be part of ADME. 

Foreign clinical results are acceptable except in areas where there are immunological and ethnic differences between Japanese and foreigners. The ethnic factors are divided into two components intrinsic factors such as racial factors and physiological differences and extrinsic factors, which include cultural and environmental issues. In these cases, the MHLW may require that some bridging comparative clinical trials be performed with dose ranging protocols. This will enable absorption, distribution, metabolism, and excretion studies to be carried out on Japanese individuals and provide better dosage and indication for the Japanese people. The MHLW also requires that application be accompanied by one year of real-time stability data and that sterility test results be included. 

The issues related to pharmacokinetics - drug absorption, distribution, metabolism, excretion - have always been important to the success of the drug discovery process. In many cases, not enough attention was paid to these factors in the early stages of the discovery... 

Pharmacokinetics (i.e. study of the movements of a medication) antipsychotics and other medications show differences in absorption, distribution, metabolism and excretion as a result of their different chemical structures and pharmaceutical preparations (capsule, tablet, injectable) and in relation to the conditions within the body (see Chapter 5). The transfer of a medication from the blood into the brain tissue across the so-called blood brain barrier, its binding to specific brain structures and thus its actions depend on the physicochemical properties of the molecule. The interplay of these and other factors explains why antipsychotics of different chemical structures are not equally effective milligram for milligram (Table 1.2 column 3) and why they differ with regard to onset and duration of action. 

One of the factors that can alter the response to drugs is the concurrent administration of other drugs. There are several mechanisms by which drugs may interact, but most can be categorized as pharmacokinetic (absorption, distribution, metabolism, excretion), pharmacodynamic (additive or antagonistic effects), or combined interactions. The general principles of pharmacokinetics are discussed in Chapters 3 and 4 the general principles of pharmacodynamics in Chapter... 

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). 

It is necessary to appreciate both for a mechanistic view of toxicology. The first of these includes the absorption, distribution, metabolism, and excretion of xenobiotics, which are all factors of importance in the toxic process and which have a biochemical basis in many instances. The mode of action of toxic compounds in the interaction with cellular components, and at the molecular level with structural proteins and other macromolecules, enzymes, and receptors, and the types of toxic response produced are included in the second category of interaction. However, a biological system is a dynamic one, and therefore a series of events may follow the initial response. For instance, a toxic compound may cause liver or kidney damage and thereby limit its own metabolism or excretion. 

The importance of the physicochemical characteristics of compounds has already been alluded to in the previous two chapters. Thus, lipophilicity is a factor of major importance for the absorption, distribution, metabolism, and excretion of foreign compounds. Lipophilic compounds are more readily absorbed, metabolized, and distributed, but more poorly excreted, than hydrophilic compounds. 

Chemical factors. Lipophilicity, polarity, and size of a molecule are all important in determining absorption, distribution, metabolism, and excretion of the chemical and hence its toxicity. The chirality of a molecule may affect its absorption, distribution, excretion, and the route of metabolism or extent to which it is metabolized and hence its toxicity. Planarity may affect the interaction with a receptor. 

The determination of a permissible exposure to a toxic substance requires evaluation of qualitative and quantitative factors including the identification and health significance of the adverse effect the sensitive members of and the size of the exposed population, biological absorption, distribution, metabolism, and excretion and the possible additivity, synergism, or antagonism with coexposed substances. 

Pharmacokinetics is the study of how the body affects an administered drug. It measures the kinetic relationships between the absorption, distribution, metabolism, and excretion of a drug. To be a safe and effective drug product, the drug must reach the desired si te of therapentic activity and exist there for the desired time period in the concentration needed to achieve the desired effect. Too little of the drug at such sites yields no positive effect (MTC) leads to toxicity. For intravenous administration there is no absorption factor. Total body elimination includes both metabolic processing and excretion. 

Pharmacokinetic The quantitative study of factors that control the time course for absorption, distribution, metabolism, and excretion of chemicals within the body. 

The pharmacokinetic phase of drug action includes the Absorption, Distribution, Metabolism and Elimination (ADME) of the drug. Many of the factors that influence drug action apply to all aspects of the pharmacokinetic phase. Solubility (see Section 3.3), for example, is an important factor in the absorption, distribution and elimination of a drug. Furthermore, the rate of drug dissolution, that is, the rate at which a solid drug dissolves in the aqueous medium, controls its activity when a solid drug is administered by enteral routes (see Section 2.6) as a solid or suspension. 

All these different factors—absorption, distribution, metabolism, and excretion—interact with each other and together determine various pharmacological parameters that have clinical significance ... 

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