Central compartment

This model consists of a total of five compartments, the drug delivery system (DDS), the gastrointestinal tract (GIT), the central compartment (Central), and two elimination compartments denoted with a dashed box outline, one for pre-systemic elimination (Unavailable) and one for... 

FIGURE 9.15 (A) First order clearance of a drug from a single compartment (central compartment). Concentration wanes,... 

The Oldshue-Rushton column (Eig. 15d) was developed (162) in the early 1950s and has been widely used in the chemical industry. It consists essentially of a number of compartments separated by horizontal stator-ring baffles, each fitted with vertical baffles and a turbine-type impeller mounted on a central shaft. Columns up to 2.74 m in diameter have been reported in service (162—167). Scale-up is reported to be reliably predictable (168) although only limited performance data are available (169). A detailed description and review of design criteria are available (170). 

Refer to Fig. 15-39. The tower is formed into compartments by horizontal doughnut-shaped or annular baffles, and within each compartment agitation is provided by a rotating, centrally located, horizontal disk. Somewhat similar devices have been known for some time. The features here are that the rotating disk is smooth and flat and of a diameter less than that of the opening in the stationaiy baffles, which facihtates fabrication and apparently improves extraction rates. The typical proportions of the internals of the RDC are as follows ... 

A central valve with bridge setting to control the various zones throughout the filtration cycle, and in some instances, two bridge circles with the second serving to purge the pan. The valve has internal compartments for the mother and wash filtrates. 

Another type of therapeutically active molecule is one designed primarily with pharmacokinetics in mind (designed to be well absorbed and to enter the central compartment readily), which can then be converted to the therapeutically active molecule in the body. These are referred to as pro-drugs. This process, called latentiation, consists of the conversion of hydrophilic drugs into lipid-soluble drugs (usually by masking hydroxyl, carboxyl, and... 

Area under the Curve (AUC) refers to the area under the curve in a plasma concentration-time curve. It is directly proportional to the amount of drug which has appeared in the blood ( central compartment ), irrespective of the route of administration and the rate at which the drug enters. The bioavailability of an orally administered drug can be determined by comparing the AUCs following oral and intravenous administration. 

Among electrochemical methods of water purification, one can also list the various electromembrane technologies, electrodialysis in particular. The simplest elec-trodialyzer consists of three compartments separated by semipermeable membranes (usually, cation- and anion-exchange membranes). The water to be purified is supplied to the central (desalination) compartment. In the outer (concentration) compartments, electrodes are set up between which a certain potential difference is applied. Under the effect of the electric field, ions pass througfi the membranes so that the concentration of ionic contaminants in the central compartment decreases. 

Aqueous solubility is not usually considered a priori as a problem in the drug discovery of acidic compounds. More important issues are (i) the high serum albumin binding of stronger acids, (ii) the very low or nonexistent central nervous system penetration of stronger acids, (iii) the low volumes of distribution of acids limiting these mostly to plasma compartment targets, (iv) the possibility of formation of... 

Fig. 39.1. Two-compartment open model composed of a central (plasma) compartment and a target (skin) compartment. This model assumes that a dmg is delivered rapidly into plasma from which it is either exchanging with the target organ or eliminated by excretion or metabolism.

Figure 39.4a represents schematically the intravenous administration of a dose D into a central compartment from which the amount of drug Xp is eliminated with a transfer constant kp. (The subscript p refers to plasma, which is most often used as the central compartment and which exchanges a substance with all other compartments.) We assume that mixing with blood of the dose D, which is rapidly injected into a vein, is almost instantaneous. By taking blood samples at regular time intervals one can determine the time course of the plasma concentration Cp in the central compartment. This is also illustrated in Fig. 39.4b. The initial concentration Cp(0) at the time of injection can be determined by extrapolation (as will be indicated below). The elimination pool is a hypothetical compartment in which the excreted drug is collected. At any time the amount excreted must be equal to the initial dose D minus the content of the plasma compartment Xp, hence ...

The AUC is a measure of bioavailability, i.e. the amount of substance in the central compartment that is available to the organism. It takes a maximal value under intravenous administration, and is usually less after oral administration or parenteral injection (such as under the skin or in muscle). In the latter cases, losses occur in the gut and at the injection sites. The definition also shows that for a constant dose D, the area under the curve varies inversely with the rate of elimination kp and with the volume of distribution V. Figure 39.6 illustrates schematically the different cases that can be obtained by varying the volume of distribution Vp and the rate of elimination k both on linear and semilogarithmic diagrams. These diagrams show that the slope (time course) of the curves are governed by the rate of elimination and that elevation (amplitude) of the curve is determined by the volume of distribution. 

This model is representative for the conditions described in the previous section, except for the mode of administration which can be oral, rectal or parenteral by means of injection into muscle, fat, under the skin, etc. (Fig. 39.7). In addition to the central plasma compartment, the model involves an absorption compartment to which the drug is rapidly delivered. This may be to the gut in the case of tablets, syrups and suppositories or into adipose, muscle or skin tissues in the case of injections. The transport from the absorption site to the central compartment is assumed to be one-way and governed by the transfer constant (Fig. 39.7a). The linear differential model for this problem can be defined in the following way ... 

The effect of incomplete absorption is that only a fraction of a single-dose D is made available to the central plasma compartment. The solution of the previous model needs, therefore, to be modified by replacing the term D by F D. Consequently the area under the curve AUCg under incomplete extravascular absorption will be smaller than the maximal AUC that results from complete absorption. The latter, as we have seen is equal to the AUC obtained from a single intravenous injection, which we denote by AUC,. These considerations can be summarized as follows ... 

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