Figure 2B: The possible sites of drug elimination duringabsorptionFigure 2B source:http://primarypsychiatry.com/2002-guide-to-psychotropic-drug-interactions/Decreased rates of drug absorption are clinicallyimportant for drugs that are given as a single dose in situations requiringrapid onset of action, for example with analgesics or hypnotics. Therefore drugconcentration can also be affected by the product formulation. As with drugsthat undergo first-pass metabolism, drugs that are incompletely absorbed afteroral administration will have much higher blood concentration when they areadministered intravenously. The intramuscular and subcutaneous administrationwill yield lower peak blood concentrations than those observed followingintravenous administration.
On the other handthe rate of absorption is usually unimportant for compounds which are given inmultiple dose regimen to achieve a desired therapeutic plasma concentration,however while the drug may be completely absorbed, this may occur so slowlythat effective blood levels are never reached, or the rate of onset may be tooslow when prompt action is required. 2.2 Serum: Tissue Concentration In order for adrug to exert its characteristic effect, it must reach its site of action. Thesite of action is where a drug acts to initiate the chain of events leading toan effect. Though it would be useful to monitor the concentration of drug atthese sites, receptor sites of drugs are generally inaccessible to ourobservations or are widely distributed in the body, therefore directmeasurement of drug concentrations at these sites is not practical (Rizk et al.
2017). For example, the receptor sites for digoxin arethought to be within the myocardium. Obviously, we cannot directly sample drugconcentration in this tissue.
However, we can measure drug concentration in theblood or serum, urine, saliva, and other easily sampled fluids (Peng and Chiou 1990). Unless a drug is purposelyadministered to produce it is effect locally, or is injected directly into thebloodstream, getting to its site of action involves two separateprocesses. The first of these isabsorption (we covered in 2.2 section of this chapter). The second process is distribution.Distribution is defined as the dispersion of a drug throughout the body so itis the process by which the drug goes from vascular space to extravascularspace.
Extravascular spaces include different compartments in the body, forexample, interstial space, fat, muscles and bone etc., so these are the spacesor volumes that should be considered when we calculate drug concentration (Figure 4)