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  • Discuss the clinical role of clearance as a PK parameter.

  • Calculate clearance using different methods including the noncompartmental, compartmental, and “physiological” approaches.

  • Define clearance and its relationship to a corresponding half-life and a volume of distribution.

  • Differentiate between total, hepatic, and renal clearances.

  • Describe the processes for renal drug excretion and explain which renal excretion process predominates in the kidney for a specific drug given its renal clearance.

  • Describe the renal clearance model based on renal blood flow, glomerular filtration, and drug reabsorption.

  • Be able to calculate if a change in hepatic or renal clearance will have a significant effect or not.

  • Describe hepatic drug clearance in terms of blood flow and extraction using the “physiologic” well-stirred model.

  • Predict the impact of a drug−drug interaction on protein binding or intrinsic clearance on the liver and total drug clearances, unbound exposure, and oral bioavailability for low and highly extracted drugs using the “physiologic” well-stirred model.


Chapter 6 discussed the physiologic aspects of drug elimination. This chapter will discuss the pharmacokinetic calculations of drug elimination including total body clearance, renal clearance, and hepatic clearance.

Drug elimination is a combination of different processes, interconnected with each other, that aim at removing the drug from the body. The major drug elimination processes include renal clearance through the kidney and hepatic clearance, which includes both biotransformation and biliary drug excretion. In general, hydrophilic, water-soluble drugs are eliminated more rapidly through the kidney than hydrophobic, lipid-soluble drugs. Many lipid-soluble drugs are metabolized in the liver by various oxidative reactions such as hydroxylation and then conjugated to form a glucuronide or sulfate metabolite. These metabolic processes transform the drug into more polar, water-soluble metabolites that are readily excreted into the urine or bile. Parent drugs may be also eliminated unchanged directly in the kidney or via biliary excretion through the liver. A clinician should consider all drug elimination processes and the importance of each process in the removal of the drug and its metabolites from the body.

In this chapter, we will focus on the diverse ways of calculating clearances, integrating liver and kidney functions, as well as understanding the elimination of parent compounds and metabolites.


Drug elimination in the body involves many complex rate processes. Although organ systems have specific functions, the tissues within the organs are not structurally homogeneous, and elimination processes may vary in each organ.

The term clearance describes the process of drug elimination from the body or from a single organ without identifying the individual processes involved. Clearance may be defined as the volume of fluid removed of the drug from the body per unit of time. The units for clearance are volume/time, sometimes in milliliters per minute (mL/min) but most often reported in liters per hour (L/h). The volume ...

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