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  • Describe the pathways for drug elimination in the body.

  • Compare the clinical implications of hepatic and renal disease on drug therapy.

  • Describe the role of hepatic blood flow, drug protein binding, and intrinsic clearance on hepatic clearance.

  • Explain how the rate of drug elimination may change from first-order elimination to zero-order elimination and the clinical implications of this occurrence.

  • Describe the biotransformation of drugs in the liver and which enzymatic processes are considered “phase I reactions” and “phase II reactions.”

  • List the organs involved in drug elimination and the significance of each.

  • Discuss the relationship between metabolic pathways and enzyme polymorphisms on intrasubject variability and drug–drug interactions.

  • Describe how the exposure of a drug is changed when coadministered with another drug that shares the same metabolic pathway.

  • Define Michaelis–Menton kinetics and capacity-mediated metabolism.

  • Calculate drug and metabolite concentrations for drugs that undergo both hepatic and biliary elimination.

  • Define first-pass metabolism and describe the relationship between first-pass metabolism and oral drug bioavailability.

  • Use urine data to calculate fraction of drug excreted and metabolized.

  • Explain how Michaelis–Menton kinetics can be used to determine the mechanism of enzyme inhibition and transporter inhibition.

  • Describe biliary drug excretion and define enterohepatic drug elimination.

  • Discuss the reasons why bioavailability is variable and can be less than 100%.

  • Describe BDDCS—Biological Drug Disposition Classification System.


The decline from peak plasma concentrations after drug administration results from drug elimination or removal by the body. The elimination of most drugs from the body involves the processes of both metabolism (biotransformation) and renal excretion (see Chapter 7). For many drugs, the principal site of metabolism is the liver. However, other tissues or organs, especially those tissues associated with portals of drug entry into the body, may also be involved in drug metabolism. These sites include the lung, skin, gastrointestinal mucosal cells, microbiological flora in the distal portion of the ileum, and large intestine. The kidney may also be involved in certain drug metabolism reactions.

Whether a change in drug elimination is more likely to be affected by renal disease, hepatic disease, or a drug–drug interaction may be predicted by measuring the fraction of the drug that is eliminated by either metabolism or excretion. Drugs that are highly metabolized (such as phenytoin, theophylline, and lidocaine) often demonstrate large intersubject variability in elimination half-lives and are dependent on the intrinsic activity of the biotransformation enzymes, which may vary by genetic and environmental factors. Intersubject variability in elimination half-lives is less for drugs that are eliminated primarily by renal drug excretion. Renal drug excretion is highly dependent on the glomerular filtration rate (GFR) and blood flow to the kidney. Since GFR is relatively constant among individuals with normal renal function, the elimination of drugs that are primarily excreted unchanged in the urine is also less variable.

First-Order Elimination


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