Body compartments

TBW depletion (often referred to as dehydration ) is typically a more gradual, chronic problem compared to ECF depletion. Because TBW depletion represents a loss of hypotonic fluid (proportionally more water is lost than sodium) from all body compartments, a primary disturbance of osmolality is usually seen. The signs and symptoms of TBW depletion include CNS disturbances (mental status changes, seizures, and coma), excessive thirst, dry mucous membranes, decreased skin turgor, elevated serum sodium, increased plasma osmolality, concentrated urine, and acute weight loss. Common causes of TBW depletion include insufficient oral intake, excessive insensible losses, diabetes insipidus, excessive osmotic diuresis, and impaired renal concentrating mechanisms. Long-term care residents are frequently admitted to the acute care hospital with TBW depletion secondary to lack of adequate oral intake, often with concurrent excessive insensible losses. 

Since the body may be viewed as a very complex system of compartments, at first it might appear to be hopeless to try to describe the time course of the drug at the receptor sites in any mathematically rigorous way. The picture is further complicated by the fact that, for many drugs, the locations of the receptor sites are unknown. Fortunately, body compartments are connected by the blood system, and distribution of drugs among the compartments usually occurs much more rapidly than absorption or elimination of the... 

An important parameter of the one-compartment model is the apparent volume of the body compartment, because it directly determines the relationship between the plasma concentration and the amount of... 

A discussion of all the reasons for this phenomenon is beyond the scope of this chapter, but a simple example will illustrate the concept. Highly lipid-soluble drugs, such as pentobarbital, are preferentially distributed into adipose tissue. The result is that plasma concentrations are extremely low after distribution is complete. When the apparent volumes of distribution are calculated, they are frequently found to exceed total body volume, occasionally by a factor of 2 or more. This would be impossible if the concentration in the entire body compartment were equal to the plasma concentration. Thus, Vd is an empirically fabricated number relating the... 

While these models simulate the transfer of lead between many of the same physiological compartments, they use different methodologies to quantify lead exposure as well as the kinetics of lead transfer among the compartments. As described earlier, in contrast to PBPK models, classical pharmacokinetic models are calibrated to experimental data using transfer coefficients that may not have any physiological correlates. Examples of lead models that use PBPK and classical pharmacokinetic approaches are discussed in the following section, with a focus on the basis for model parameters, including age-specific blood flow rates and volumes for multiple body compartments, kinetic rate constants, tissue dosimetry,... 

Description of the model. The Leggett Model includes a central compartment, 15 peripheral body compartments, and 3 elimination pools, as illustrated in Figure 2-9. Transport of lead between... 

The anti-ulcer agents omeprazole, lanzoprazole, and pantoprazole have been introduced during the past decade for the treatment of peptic ulcers. Gastric acid secretion is efficiently reduced by prazole inhibition of H+K+-ATPase in the parietal cells of the gastrointestinal mucosa [75]. The prazoles themselves are not active inhibitors of the enzyme, but are transformed to cyclic sulfenamides in the intracellular acidic compartment of parietal cells [76]. The active inhibitors are permanent cations at pH < 4, with limited possibilities of leaving the parietal cells, and thus are retained and activated at the site of action. In the neutral body compartments the prazoles are stable, and only trace amounts are converted to the active drugs. (For a review on omeprazole, see Ref. [77].)... 

Cartwright [124] reported that miconazole was slightly absorbed from epithelial and mucosal surface. The drug is well absorbed from the gastrointestinal tract, but caused nausea and vomiting in some patients. The drug may be given intravenously but was associated phlebitis. Up to 90% of the active compound was bound to plasma protein. Distribution into other body compartments was poor. Metabolism was primarily in the liver, and only metabolites were excreted in the urine. At therapeutic levels, they were relatively nontoxic both locally and systematically, but occasionally produced disturbances on the central nervous system. 

The terminology for the so-called central compartment is Q. There are various rate constants that should be included in the diagram K01 is the rate constant for a drug moving from the outside of the body (compartment 0) to the central compartment (compartment 1) K10 is the rate constant of elimination from Ci to C o- Single-compartment models do not occur physiologically. 

Continuous monitoring of organ function displays in real-time the clearance profile or concentration of an organ function-specific marker in a pre-deter-mined body compartment. This approach allows the early intervention by clinicians since instantaneous deviation from the established baseline reading may indicate the onset of an anomaly. However, it may not be useful for measuring dynamic functional reserve of the organ because subsequent activities after marker elimination from plasma may not be reflected in the clearance profile. 

Gases diffuse from areas of high partial pressure to areas of low partial pressure thus, the tension of anesthetic in the alveoli provides the driving force to establish brain tension. In fact, the tension of anesthetic in all body tissue will tend to rise toward the lung tension as equilibrium is approached. Consequently, factors that control or modify the rate of accumulation of anesthetic in the lung (e.g., rate of gas delivery, uptake of gas from the lung into the pulmonary circulation) will simultaneously influence the rate at which tension equilibria in other body compartments is established. 

L D. Excretion (A) and drug clearance (E) are factors involved in drug elimination, while absorption (B) describes the ability of a drug to cross membranes and enter the blood stream. Distribution (C) describes the ability of a drug to enter a variety of body compartments during its circulation in the blood. 

There are four main compartments a soluble macromolecule can enter the central compartment (blood and lymphatic system), interstitium, intestinal lumen, and lysosomes [100, 101]. Minor compartments are primary urine, liquor, bile, etc. There is no experimental evidence that clearly indicates the penetration of synthetic macromolecules into the cytoplasm, i.e, into the intracellular compartment (inside the cell but outside the endosomes or lysosomes) [101]. The movements of soluble macromolecules between body compartments have been extensively reviewed [14, 20,100-104] and will not be covered in detail here. We shall concentrate on the discussion of main factors influencing the movement of soluble macromolecules when administered into the bloodstream. Depending on the structure and molecular weight distribution, part of the polymeric molecules are excreted in the urine. Simultaneously, the macromolecules are cleared from the bloodstream by endocytosis. It is important to note that nonspecific capture of soluble macromolecules by the specialized cells of the reticuloendothelial system is generally much less (orders of magnitude) when compared to vesicular carriers of a comparable structure. 

Because plasma protein and tissue binding influences the amount of drug in each body compartment, the volume of distribution of a drug may be dose dependent (nonhnear). A limited number of binding sites may result in capacity-limited binding in plasma or tissues. Transport from the blood may also be capacity limited. Examples of dose-dependent volume changes show that the volume of distribution of recombinant human tumor necrosis factor (TNF) alpha decreases sharply with a fourfold increase in dose and that the volume of distribution of recombinant human DNase,... 

Distribution of the drug is conceptualized as accumulation into various body compartments (e.g., fat, aqueous, bone, brain, etc.). The extent to which drugs differ in their rate and degree of accumulation into various organs is related to the number of compartments into which they equilibrate. Even within one apparent compartment, such as blood, there may be more than one subcomponent for distribution, including the following ... 

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