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The pharmacokinetics of drugs following intravenous drug administration are simpler to model compared to extravascular delivery (see Chapters 16). Extravascular delivery routes, particularly oral dosing, are important and popular means of drug administration. Unlike intravenous administration, in which the drug is injected directly into the plasma, pharmacokinetic models after extravascular drug administration must consider systemic drug absorption from the site of administration, for example, the lung, the gut, etc, into the plasma. Extravascular drug delivery is further complicated by variables at the absorption site, including possible drug degradation, metabolism, and significant inter- and intrapatient differences in the rate and extent of absorption. Absorption and metabolic variables are characterized using pharmacokinetic methods. The variability in systemic drug absorption can be minimized to some extent by proper biopharmaceutical design of the dosage form to provide predictable and reliable drug therapy (see Chapters 1416). The major advantage of intravenous administration compared to extravascular drug absorption is that the rate and extent of systemic drug input are carefully controlled.

The systemic drug absorption from the gastrointestinal (GI) tract or from any other extravascular site is dependent on (1) the physicochemical properties of the drug, (2) the type and design of dosage form, and (3) the anatomy and physiology of the drug absorption site. Although this chapter will focus primarily on oral dosing, the concepts discussed here may be extrapolated to other extravascular routes. For oral dosing, such factors as surface area of the GI tract, stomach-emptying rate, GI mobility, and blood flow to the absorption site all affect the rate and the extent of drug absorption. In pharmacokinetics, the overall rate of drug absorption may be described as either a first-order or zero-order input process. Most pharmacokinetic models assume first-order absorption unless an assumption of zero-order absorption improves the model significantly or has been verified experimentally.

The rate of change in the amount of drug in the body, dDB/dt, is dependent on the relative rates of drug absorption and elimination (Fig. 7-1). The net rate of drug accumulation in the body at any time is equal to the rate of drug absorption less the rate of drug elimination, regardless of whether absorption rate is zero order or first order.


where DGI is the amount of drug in the gastrointestinal tract and DE is the amount of drug eliminated. A plasma level–time curve showing drug absorption and elimination rate processes is given in Fig. 7-2. During the absorption phase of a plasma level–time curve (Fig. 7-2), the rate of drug absorption1 is greater than the rate of drug elimination.2 Note that during the absorption phase, elimination occurs whenever drug is present in the plasma, even though absorption predominates.


Figure 7-1

Model of drug absorption and ...

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