The process of drug absorption

Drags administered orally must cross the GI tract epithelium to be absorbed and enter the systemic circulation. Similarly, drags administered by alternative routes, such as the buccal, sublingual, nasal, pulmonary and vaginal routes, must all cross the appropriate epithelial interfaces to reach the general circulation. The types of epithelial interfaces, the barriers they pose to drag absorption, and the routes and mechanisms of drag absorption across these interfaces, are described below. 

The epithelia are a diverse group of tissues, which, with rare exceptions, line all body surfaces, cavities and glands. They consist of one or more layers of cells, separated by a minute quantity of intercellular material. All epithelia are supported by a basement membrane of variable thickness, which separates the epithelium from underlying connective tissues. 

Epithelial interfaces are involved in a wide range of activities such as absorption, secretion and protection all these major functions may be exhibited at a single epithelial surface. For example, the epithelial lining of the small intestine is primarily involved in absorption of the products of digestion, but the epithelium also protects itself from potentially harmful substances by the secretion of a surface coating of mucus. 

Epithelia are classified according to three morphological characteristics  

A single layer of epithelial cells is termed simple epithelium, whereas those composed of more than one layer are termed stratified epithelia. Stratified epithelia are found in areas which have to withstand large amounts of wear and tear, for example the inside of the mouth, orthe skin. Epithelial cells may be, for example, squamous (flattened), columnar (tall), cuboidal (intermediate between squamous and columnar) and may contain surface specializations, such as cilia in the nasal epithelium and keratin in the skin. 

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This generally describes the process of drug absorption into the body, distribution throughout the body, metabolism by degrad a tive and metabolizing enzymes in the body, and finally elimination from the body. It is useful to consider each of these steps because together they summarize pharmacokinetics. 

The hyperbolic relationship be tween plasma concentration and effect explains why the time course of the effect, unlike that of the plasma concentration, cannot be described in terms of a simple exponential function. A half-life can be given for the processes of drug absorption and elimination, hence for the change in plasma levels, but generally not for the onset or decline of the effect... 

Pharmacokinetics What the body does to the drug. The process of drug absorption from the site of administration, distribution to the target organ and other bodily compartments, metabolism or biotransformation (if necessary), and eventual elimination. 

As the examples cited above indicate, many clinical chug interactions have been considered to be mediated by inhibition or induction of transporters based only on circumstantial evidence. Because of the lack of potent and specific inhibitors for each transporter, it is difficult to accurately assess the relative contributions CYP enzymes and transporters in drug absorption and excretion. The mechanisms become even more complex when multiple CYP enzymes and drug transporters are involved in the processes of drug absorption and excretion. Therefore, care should be taken when exploring the underlying mechanism of drug interactions. 

The process of drug absorption has been described above and a brief description of the processes of distribution, metabolism and excretion are given below, with particular reference to their influence on drag... 

Pharmacokinetics is defined as the quantitative analysis of the processes of drug absorption, distribution, and elimination that determine the time course of drug action. Pharmacodynamics deals with the mechanism... 

The rationaie for measuring concentrations of drugs in piasma, serum, or biood is that concentration-response reiationships are often iess variabie than are dose-response reiationships (2). This is true because indi-viduai variation in the processes of drug absorption, distribution, and eiimination affects dose-response reiationships, but not the reiationship between free (nonprotein-bound) drug concentration in piasma water and intensity of effect (Figure 2.1). 

FIGURE 4.8 The processes of drug absorption and disposition (distribution and elimination) interact to generate the observed time course of drug in the body. Similarly, the output function can be represented as an interaction betw een absorption and disposition functions. 

One can now appreciate why conventional definitions of pharmacokinetics are a little different from the definition given here. The conventional definitions make references to events other than temporal and spatial distribution. These events are, in fact, consequences of a drug s kinetics, and thus the two should be separated. The processes of drug absorption, distribution, metabolism, and elimination relate to parameters that can only be estimated from a mathematical model describing the kinetics of the drug. The point is that, to understand the mathematical basis of pharmacokinetic parameter estimation, it is necessary to keep in mind the separation between kinetics per se and the use of data to estimate pharmacokinetic parameters. 

In summary, the processes of drug absorption and distribution illustrate that a drug is a chemical that, when introduced into the body, disrupts its steady biochemical state. Absorption and distribution are the complex fundamentals of bioavailability, or how much drug reaches its sites of action. Bioavailability tells us most about drug effects. To understand the effects of a drug over time, it is essential to track its excretion or elimination from the body. 

FIGURE 12.4 Schematic representation of the process of drug absorption following oral... 

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