Pharmacokinetic processes

Drags differ in their intrinsic ability to produce an effect, in their ability to reach the site of action and in their rate of removal from that site. Pharmacodynamics is the study of the action of the drag on the body. Pharmacokinetics is the study of how drugs enter the body, reach the site of action and are removed from the body, i.e. the study of  

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 

Many drags show an affinity for specific binding sites on plasma proteins such as albumin and a]-acid glycoprotein, which results in a reversible association, with some important consequences in therapeutics  

A particular repercussion of the process of drug distribution is that after administration of a drug, unwanted drug disposition may occur, either  

This can result in the need to use high doses to compensate for drag wasteage, which is expensive. Unwanted deposition may also result in toxicity problems, arising from drag action at non-target sites. 

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The receptor represents the locus of dmg action. However, the pharmacokinetic processes of absorption (dmg entry), distribution, metaboHsm, and excretion play principal roles in determining in vivo time courses and concentrations of dmgs and thus modify actions initiated at receptors. 

FIGURE 8.21 Schematic representation of the pharmacokinetic processes involved in drag absorption, distribution, and elimination. 

Pharmacokinetics. Figure 1 Main pharmacokinetic processes and parameters Half-life (T1/2), volume (Vd), elimination rate constant (Ke), and clearance (Cl). 

Leung 1993). PBPK models for a particular substance require estimates of the chemical substance-specific physicochemical parameters, and species-specific physiological and biological parameters. The numerical estimates of these model parameters are incorporated within a set of differential and algebraic equations that describe the pharmacokinetic processes. Solving these differential and algebraic equations provides the predictions of tissue dose. Computers then provide process simulations based on these solutions. 

On some occasions, the body does not behave as a single homogeneous compartment, and multicompartment pharmacokinetics are required to describe the time course of drug concentrations. In other instances certain pharmacokinetic processes may not obey first-order kinetics and saturable or nonlinear models may be required. Additionally, advanced pharmacokinetic analyses require the use of various computer programs, such as those listed on the website http //www.boomer.org/pkin/soft.html. 

During the past decade, numerous articles reviewing the effects of aging on pharmacokinetic processes (i.e., absorption, distribution, metabolism, and elimination) have been published [115 124h]. An outline of the observations made in these reports is supplied in Table 5. The absorption process is the only process that will be covered in depth in this chapter, as this is the process that can most easily be manipulated through formulation techniques. 

Table 5 Changes in Pharmacokinetic Processes Observed with Aging... 

There are many prevalent conditions in the elderly that can interfere with the normal pharmacokinetic process. The changes in the gastrointestinal tract due to aging do not normally give any problems with drug treatment but in combination with diverse chronic ailments, they do. The absorption of drugs can be disturbed by the... 

The study of ADME had its origins in pharmacology, the science of drugs. Because these processes involve rates of different types, this area of study came to be called pharmacokinetics The combined effects of these pharmacokinetic processes determine the concentration a particular chemical (the chemical entering the body or one or more of its metabolites) will achieve in various tissues and cells of the... 

The pharmacokinetic processing of macromolecules used as targeting devices or drug carrier systems is different from that of conventional cytotoxic drugs and plays an important role in e.g. the targeting efficiency of these cytotoxic agents coupled to the macromolecules. 

Box 5.1 The pharmacokinetic processes Absorption - the process of getting drug into the body (not necessarily the systemic circulation) Distribution - the processes of distribution into fluids and tissues... 

Pharmacokinetic interactions may occur during one or more of the pharmacokinetic processes whereby the drug reaches its site of action and is then eliminated (i.e. absorption, distribution, metabolism and excretion). Such interactions may result in a change in the drug concentration at the site of action with subsequent toxicity or decreased efficacy. 

Several nonsedative Hj inhibitors have been marketed—for example, astemizole (4.149) and terfenadine (4.150). They are quite polar molecules and therefore cannot cross the blood-brain barrier to reach central histamine receptors. This is a good example of drug design exploiting knowledge of the pharmacokinetic processes to preclude undesirable CNS side effects. 

Pharmacokinetic processes govern the absorption, distribution, and elimination of drugs and are of great practical importance in the choice and administration of a particular drug for a particular patient, eg, a patient with impaired renal function. The following paragraphs provide a brief introduction to pharmacodynamics and pharmacokinetics. 

This equation has a concentration term, C0, indicating that the half-life is variable and dependent on drug concentration. Changes in pharmacokinetic parameters that occur as a function of dose or drug concentration are referred to as nonlinear pharmacokinetic processes. Nonlinearity is usually due to saturation of protein binding, hepatic metabolism, or active renal transport of the drug.3... 

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