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CHAPTER OBJECTIVES

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  • Describe a one-compartment model, IV bolus injection.

  • Provide the pharmacokinetic terms that describe a one-compartment model, IV bolus injection, and the underlying assumptions.

  • Explain how drugs follow one-compartment kinetics using drug examples that follow one-compartment kinetics.

  • Calculate pharmacokinetic parameters from drug concentration–time data using a one-compartment model.

  • Simulate one-compartment plasma drug level graphically using the one-compartment model equation.

  • Calculate the IV bolus dose of a drug using the one-compartment model equation.

  • Relate the relevance of the magnitude of the volume of distribution and clearance of various drugs to underlying processes in the body.

  • Derive model parameters from slope and intercept of the appropriate graphs.

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While the oral route of drug administration is the most convenient, intravenous (IV) administration is the most desirable for critical care when reaching desirable drug concentrations quickly is needed. Examples of when IV administration is desirable include antibiotic administration during septic infections or administration of antiarrhythmic drugs during a myocardial infarction. Because pharmacokinetics is the science of the kinetics of drug absorption, distribution, and elimination, IV administration is desirable in understanding these processes since it simplifies drug absorption, essentially making it complete and instantaneous. This leaves only the processes of drug distribution and elimination left to study. This chapter will introduce the concepts of drug distribution and elimination in the simplest model, the one-compartment open model.

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The one-compartment open model assumes that the body can be described as a single, uniform compartment (ie, one compartment), and that drugs can enter and leave the body (ie, open model). The simplest drug administration is when the entire drug is given in a rapid IV injection, also known as an IV bolus. Thus, the one-compartment open model with IV bolus administration is the simplest pharmacokinetic model. It assumes that the drug is administered instantly into the body, it is instantaneously and rapidly distributed throughout the body, and drug elimination occurs immediately upon entering the body. This model is a simplistic representation of the processes in the body that determine drug disposition, but nonetheless, it can be useful to describe and predict drug disposition.

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In reality, when a drug is administered intravenously, the drug travels through the bloodstream and distributes throughout the bloodstream in the body. While this process is not truly instantaneous, it is relatively rapid enough that we can make this assumption for most drugs. Through the bloodstream, the drug is distributed to the various tissue organs in the body. The rate and extent of distribution to the tissue organs depends on several processes and properties. Tissues in the body are presented the drug at various rates, depending on the blood flow to that organ, and the drug may have different abilities to cross from the vasculature to the organ depending on the molecular weight of the drug. Tissues also have different affinity for the drug, depending on lipophilicity and drug binding. Finally, large organs may have a large ...

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