Intravenous bolus administration loading dose

Aprotinin is not effective after oral administration, but is administered intravenously as a loading dose followed by a continuous infusion. Its activity is expressed as kallikrein inactivation units (KIU). The conventional (Munich) dose regimen consists of an initial 2 x 10 KIU bolus, a similar initial dose to prime the bypass machine, and then 0.5 x 10 KIU/ hour by continuous infusion thereafter. The half-life of aprotinin is about 2 hours. Plasma concentrations of 125 KlU/ml are necessary to inhibit plasmin, but a... 

Lidocaine follows a two-compartment model. The volume of distribution and Vss) varies with concomitant diseases or conditions as shown below. Loading doses, based on 1/, are adjusted depending on concomitant disease because the cardiovascular and central nervous systems behave as though they were located in the central compartment. Following intravenous bolus administration lidocaine concentrations fall rapidly (Ty2a = 8 min). ... 

Figure 11.11 A plot of plasma concentration (Cp) versus time following repetitive intravenous bolus administration of a drug. The figure demonstrates the plasma level resulting from either a series of maintenance doses (dashed line) or an initial loading dose followed by a series of maintenance doses (continuous line), min, minimum max, maximum MTC, minimum toxic concentration MEC, minimum effective concentration t, dosing interval.

Because considerable time may elapse before a steady-state condition is attained as a result of repeated drug administration, it often is desirable to administer a large dose initially (i.e., loading dose) to achieve the desired drug levels immediately. Equation 9.42, which describes the time course of drug concentration after a single intravenous bolus dose, may be written as... 

This is best accomplished by giving an intravenous bolus as a loading dose and then titrating the level using a continuous infusion. The rectal administration of aminophylline solution can also rapidly achieve therapeutic blood levels. Asthmatics who are prone to attacks of asthma can successfully utilize this route of administration instead of intravenous therapy. 

Figures lO.lOand 10.11, respectively, showthe predicted and real plasma concentration versus time profiles following the administration of a drug as an intravenous bolus loading dose immediately followed by an infusion.

It may take a long time and the administration of many doses (over seven or eight) before the desired "average" steady-state drug concentration is attained. Therefore, an intravenous bolus loading dose (DJ may be administered to obtain an instant steady-state condition. The calculated loading dose should be such that that, at time t after its administration, the plasma concentration of drug is the desired minimum plasma concentration at steady state, that is ... 

In this example, therefore, administration of 1018 mg procainamide HQ as a intravenous loading dose followed by the intravenous bolus maintenance dose of 557 mg every 4h will attain and then maintain an average procainamide plasma concentration of 6pgmL . ... 

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