Chapter 2: Pharmacokinetics

INTRODUCTION

This chapter will be most useful after having a basic understanding of the material in Chapter 2, Pharmacokinetics in Goodman & Gilman’s The Pharmacological Basis of Therapeutics, 12th Edition. This chapter also draws from content in Chapter 5, Membrane Transporters and Drug Response; Chapter 6, Drug Metabolism; and parts of Chapter 7, Pharmacogenetics. The drugs presented in this chapter are used to illustrate general pharmacokinetic principles. The pharmacokinetic, pharmacodynamic, and therapeutic uses of drugs described in Chapter 2 are discussed in more detail in subsequent chapters. Neither a Mechanisms of Action Table nor a Clinical Summary Table is included in this chapter because this information is provided in subsequent chapters.

In addition to the material presented here, the 12th Edition contains:

• A review in Chapter 2 of cell membranes and their physicochemical properties that affect the movement of drugs to their site of action

• A discussion in Chapter 2 of different routes of drug administration and their relative advantages and disadvantages

• A detailed discussion in Chapter 2 of renal drug excretion, biliary and fecal excretion, and excretion by other routes

• A comprehensive discussion of design and optimization of dosage regimens in Chapter 2, including examples of dosing calculations that take into consideration bioavailability, clearance, and distribution

• Appendix II Design Optimization of Dosage Regimens: Pharmacokinetic Data in Goodman & Gilman’s The Pharmacological Basis of Therapeutics, 12th Edition provides a summary of basic pharmacokinetic data for a number of drugs that are in common clinical use, as well as information that is useful in individualizing dosing in a given patient

• Chapter 5 contains a detailed review of membrane transporters, including their role in absorption, distribution, and clearance of xenobiotics, and their role in adverse drug responses

• Table 5-1 Regulation of Transporter Expression by Nuclear Receptors provides detailed information about drug regulation of transporter expression mediated through specific nuclear receptors

• A description in Chapter 5 of the role of efflux transporters in the blood-brain barrier (BBB) and blood-cerebrospinal fluid (CSF) barrier

• Chapter 6 provides a comprehensive discussion of drug metabolism enzymes and illustrations that show many of the key chemical reactions catalyzed by these enzymes

LEARNING OBJECTIVES

• Understand key concepts and terms that determine drug pharmacokinetics, including absorption, distribution, metabolism, and excretion.

• Understand the mechanisms by which drugs cross membranes and the physicochemical factors that influence this transfer.

• Be able to predict the ionization state of a drug that is a weak acid or base knowing the drug’s pK_a and the pH of the fluid.

• Describe the role of membrane transporters in drug absorption, distribution, and clearance.

• Know the major mechanisms by which drugs are metabolized and excreted from the body.

• Understand the major pharmacokinetic mechanisms that can result in drug interactions.

• Know the pharmacokinetic mechanisms that give rise to interpatient variability in drug response and toxicity.

• Understand the clinical pharmacokinetic principles used to calculate ...