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CHAPTER OBJECTIVES

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  • Define passive and active drug absorption.

  • Explain how Fick’s law of diffusion relates to passive drug absorption.

  • Calculate the percent of drug nonionized and ionized for a weak acid or weak-base drug using the Henderson–Hasselbalch equation, and explain how this may affect drug absorption.

  • Define transcellular and paracellular drug absorption and explain using drug examples.

  • Describe the anatomy and physiology of the GI tract and explain how stomach emptying time and GI transit time can alter the rate and extent of drug absorption.

  • Explain the effect of food on gastrointestinal physiology and systemic drug absorption.

  • Describe the various transporters and how they influence the pharmacokinetics of drug disposition in the GI tract.

  • Explain the pH-partition hypothesis and how gastrointestinal pH and the pKa of a drug may influence systemic drug absorption. Describe how drug absorption may be affected by a disease that causes changes in intestinal blood flow and/or motility.

  • List the major factors that affect drug absorption from oral and nonoral routes of drug administration.

  • Describe various methods that may be used to study oral drug absorption from the gastrointestinal transit.

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DRUG ABSORPTION AND DESIGN OF A DRUG PRODUCT

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Major considerations in the design of a drug product include the therapeutic objective, the application site, and systemic drug absorption from the application site. If the drug is intended for systemic activity, the drug should ideally be completely and consistently absorbed from the application site. In contrast, if the drug is intended for local activity, then systemic absorption from the application should be minimal to prevent systemic drug exposure and possible systemic side effects. For extended-release drug products, the drug product should remain at or near the application site and then slowly release the drug for the desired period of time. The systemic absorption of a drug is dependent on (1) the physicochemical properties of the drug, (2) the nature of the drug product, and (3) the anatomy and physiology of the drug absorption site.

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In order to develop a drug product that elicits the desired therapeutic objective, the pharmaceutical scientist must have a thorough understanding of the biopharmaceutic properties of the drug and drug product and the physiologic and pathologic factors affecting drug absorption from the application site. A general description of drug absorption, distribution, and elimination is shown in Fig. 14-1. Pharmacists must also understand the relationship of drug dosage to therapeutic efficacy and adverse reactions and the potential for drug–drug and drug–nutrient interactions. This chapter will focus on the anatomic and physiologic considerations for the systemic absorption of a drug, whereas Chapters 15, 16, 17, 18 will focus on the biopharmaceutic aspects of the drug and drug-product design including considerations in manufacturing and performance tests. Since the major route of drug administration is the oral route, major emphasis in the chapter will be on gastrointestinal drug absorption.

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FIGURE 14-1

The interrelationship ...

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