Drug Therapy Concepts of Elimination Half-Life and Clearance

Continuation of Drug Therapy (Concepts of Elimination Half-Life and Clearance) 

It is convenient to characterize the elimination of drugs with first-order elimination rates by their elimination half-life, the time required for half an administered drug dose to be eliminated. If drug elimination half-life can be estimated for a patient, it is often practical to continue therapy by administering half the loading dose at an interval of one elimination half-life. In this way, drug elimination can be balanced by drug 

FIGURE 2.6 Expected digoxin plasma concentrations after administering perfectly matched loading and maintenance doses (solid line), no initial loading dose (bottom dashed line), or a loading dose that is large in relation to the subsequent maintenance dose (upper dashed line). 

When intermittent oral or parenteral doses are administered at a dosing interval r, the corresponding equation is 

Since there is a directly proportionate relationship between administered drug dose and steady-state plasma levels Equations 2.2 and 2.3 provide a straightforward guide to dose adjustment for drugs that are eliminated by first-order kinetics. Thus, to double the plasma levels the dose simply should be doubled. Con-versely to halve the plasma level, the dose should be halved. It is for this reason that Equations 2.2 and 2.3 are the most clinically important pharmacokinetic equations. Note that, as is apparent from Eigure 2.6, these equations also stipulate that the steady-state level is determined only by the maintenance dose and elimination clearance. The loading dose does not appear in the equations and does not influence the eventual steady-state level. 

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