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CHAPTER OBJECTIVES

  • Discuss the clinical relevance of IV bolus injection and introduce concepts of the one-compartment linear model with this route of administration.

  • Define volume of distribution, elimination rate constant, and clearance, and explain how to calculate these parameters in a one-compartment linear model with IV bolus injection.

  • Explain the clinical utility of the one-compartment model

INTRODUCTION

Intravenous Bolus Administration

Intravenous (IV) bolus injection is a method of parenteral drug administration. The term parenteral is derived from the Greek words para (ie, beside or near) and enteron (ie, the intestine). In medicine, parenteral refers to the administration of a drug through a route that does not involve gastrointestinal absorption. IV bolus injection is the administration of an entire dose of medicine into the veins over a short period of time (less than 1 minute). Intravenous administration is the most direct route of drug administration because absorption processes are bypassed when a drug is deposited directly into the bloodstream (ie, systemic circulation). Furthermore, bolus injection is the fastest method of IV drug administration, compared to IV infusion (see Chapter 14). This quality of complete and instantaneous absorption has its advantages and disadvantages.

A therapeutic effect may be seen almost immediately with IV bolus injection because the entire dose of medication enters the bloodstream directly, skipping absorption processes, and is thereby distributed throughout the body via the systemic circulation. For this reason, IV bolus injection is preferred in emergency situations where it is critical to reach therapeutic levels quickly (eg, heart attack, stroke, or narcotic overdose). Another benefit to IV bolus injection is that it can be used when a drug is not able to be absorbed by the gastrointestinal tract or when a patient cannot receive oral medication (eg, unable to swallow or unconscious). Alternatively, an IV bolus preparation would be selected if a clinician does not have the appropriate equipment to administer an IV infusion and it is safe to administer the drug quickly.

The rapid onset of effects following IV bolus injection can be harmful if the patient has an adverse reaction, and it is too late to stop the injection and impossible to retrieve the medication once it has been administered. Higher concentrations of drug in systemic circulation (higher Cmax and early AUC exposure) are achieved following IV bolus injection compared to other routes of administration, because the entire dose is deposited directly into the bloodstream rapidly. This can result in unnecessary exposure to a drug because a large portion of the dose contributes to systemic concentrations that are higher than what is needed for a therapeutic effect, and if the drug is eliminated rapidly, then the duration of the therapeutic effect will be shorter after IV bolus injection compared to IV infusion (Fig. 12-1). These higher concentrations increase the risk of negative side effects without improving ...

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