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  • Describe the concept of steady state and how it relates to continuous dosing.

  • Determine optimum dosing for an infused drug by calculating pharmacokinetic parameters from clinical data.

  • Calculate loading doses to be used with an intravenous infusion.

  • Describe the purpose of a loading dose.

  • Compare the pharmacokinetic outcomes and clinical implications after giving a loading dose for a drug that follows a one-compartment model to a drug that follows a two-compartment model.

Drugs may be administered to patients by oral, topical, parenteral, or other various routes of administration. Examples of parenteral routes of administration include intravenous, subcutaneous, and intramuscular. Intravenous (IV) drug solutions may be either injected as a bolus dose (all at once) or infused slowly through a vein into the plasma at a constant rate (zero order). The main advantage for giving a drug by IV infusion is that it allows precise control of plasma drug concentrations to fit the individual needs of the patient. For drugs with a narrow therapeutic window (eg, heparin), IV infusion maintains an effective constant plasma drug concentration by eliminating wide fluctuations between the peak (maximum) and trough (minimum) plasma drug concentration. Moreover, the IV infusion of drugs, such as antibiotics, may be given with IV fluids that include electrolytes and nutrients. Furthermore, the duration of drug therapy may be maintained or terminated as needed using IV infusion.

The plasma drug concentration-time curve of a drug given by constant IV infusion is shown in Fig. 6-1. Because no drug was present in the body at zero time, drug level rises from zero drug concentration and gradually becomes constant when a plateau or steady-state drug concentration is reached. At steady state, the rate of drug leaving the body is equal to the rate of drug (infusion rate) entering the body. Therefore, at steady state, the rate of change in the plasma drug concentration dCp/dt = 0, and



Plasma level-time curve for constant IV infusion.

Based on this simple mass balance relationship, a pharmacokinetic equation for infusion may be derived depending on whether the drug follows one- or two-compartment kinetics.


The pharmacokinetics of a drug given by constant IV infusion follows a zero-order input process in which the drug is directly infused into the systemic blood circulation. For most drugs, elimination of drug from the plasma is a first-order process. Therefore, in this one-compartment model, the infused drug follows zero-order input and first-order output. The change in the amount of drug in the body at any time (dDB/dt) during the infusion is the rate of input minus the rate of output.


where DB is the amount of drug in the ...

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