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  • Define oral drug absorption and describe the absorption process.

  • Introduce two general approaches used for studying absorption kinetics and their similarities and differences.

  • Understand the basic principles for physiologically based absorption kinetics.

  • Describe the oral one-compartment model and explain how this model simulates drug absorption from the gastrointestinal tract.

  • Calculate the pharmacokinetic parameters of a drug that follows the oral one-compartment model.

  • Calculate the fraction of drug absorbed in a one-compartment model using the Wagner–Nelson method.

  • Calculate the fraction of drug absorbed in a two-compartment model using the Loo–Riegelman method.

  • Describe the conditions that may lead to flip-flop of ka and k during pharmacokinetics (PK) data analysis.

  • Describe the model parameters that form the foundation of drug absorption and bioavailability of oral dosage forms.

  • Discuss how ka and k may influence Cmax, tmax, and AUC and how changes in these parameters may affect drug safety in a clinical situation.




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 general circulation (see Chapters 4, 5, 6, 7), pharmacokinetic models after extravascular drug administration must consider drug absorption from the site of administration, for example, the gut, the lung, etc.


The aim of this chapter is to study the kinetics of absorption. Before delving into the details, it is important to clarify the definition of absorption.


There are three different definitions of absorption in existence. Traditionally, absorption occurs when drug reaches the systemic circulation, or sometimes when it reaches the portal vein blood stream. In recent years, a new definition is presented, in which drug is assumed to be absorbed when it leaves the lumen and crosses the apical membrane of the enterocytes lining the intestine (GastroPlus manual). It is important to distinguish among these definitions when the kinetics study is performed, especially during comparisons of the study results.


Drug absorption from the gastrointestinal (GI) tract or any other extravascular site is dependent on (1) the physicochemical properties of the drug and the environment in the small intestine, (2) the dosage form used, and (3) the anatomy and physiology of the absorption site, such as surface area of the GI tract, stomach-emptying rate, GI mobility, and blood flow to the absorption site. Extravascular drug delivery is further complicated by variables at the absorption site, including possible drug degradation and significant inter- and intrapatient differences in the rate and extent of absorption. The variability in drug absorption can be minimized to some extent by proper biopharmaceutical design of the dosage form to provide predictable and reliable drug therapy (Chapters 15, 16, 17, 18). Although this chapter will focus primarily on oral dosing, the concepts discussed here may be easily extrapolated to other extravascular routes.


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