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CHAPTER OBJECTIVES

  • Define oral drug absorption and its relevance.

  • Describe different absorption rate processes (eg, first- and zero-order).

  • Calculate the pharmacokinetic parameters of an orally administered drug that is described by a one-compartment model.

  • Calculate the absorption rate constant for an orally administered drug that is described by a two-compartment pharmacokinetic model.

  • Contrast current methods for characterizing absorption against historical methods.

  • Describe flip-flop kinetics for oral extended-release drug products.

  • Discuss the clinical implication of absorption half-life.

  • Discuss how ka and kel influence Cmax, tmax, and AUC.

  • Discuss how changes in these parameters affect drug safety in a clinical situation.

INTRODUCTION

Extravascular delivery routes are an important and popular means of drug administration and include all routes that are not intravenous (eg, oral, topical, intranasal, inhalation, intramuscular, and rectal). The route of drug administration that is chosen must be one that provides optimal therapeutic activity and safety for the patient (Chapter 7). With intravenous administration, the entire drug dose is injected directly into the systemic circulation. Drugs given by extravascular administration must first be absorbed from the site of administration. For example, after oral drug administration, the drug may be absorbed through the small intestine, whereas after inhalation, some of the drug will be absorbed after passing through the lung. The physiological aspects of drug absorption are discussed in Chapter 4. Pharmacokinetic characterization of drug absorption is important for the determination of drug exposure and the development of drug dosage regimens.

The oral route is the most common method of extravascular drug administration. The oral route is a safe, easy, and convenient method of drug administration. After drug products are given by the oral route, the drug must first be released from the drug product and dissolve in the fluids of the gastrointestinal (GI) tract for systemic drug absorption through the intestinal epithelium. In the case of oral drug solutions, this dissolution step is unnecessary as the drug is already in solution. Drug absorption is influenced by various physiological factors related to the GI tract (Chapter 4). The bioavailability of the drug is influenced by all the processes that allow the drug to reach the systemic circulation, including drug release from the drug product, dissolution into the fluids of the GI tract, transporters in the GI tract, passage of the drug through the gut wall, metabolism, and passage through the liver via the hepatic portal vein and then into the systemic circulation (Fig. 16-1).

FIGURE 16-1

Systemic drug absorption and bioavailability.

This chapter will focus on the pharmacokinetics of drug absorption following oral administration, explain the different methods that can be used to characterize and quantify drug absorption and bioavailability, and focus on the determination of absorption rate constants.

Oral ...

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