(1994; 115 pages) [French] [Spanish]
Stopping drug treatment
For drugs with first-order elimination kinetics the plasma concentration decreases by 50% each half-life period, if no more of the drug is taken (Figure 18). The effect of the drug stops when the concentration falls below the therapeutic threshold. For example, if the initial plasma concentration is 300 ug/ml, the therapeutic threshold 75 ug/ml and the half-life 8 hours, this will take 16 hours (2 half-lives). This principle applies equally to drugs taken in overdose.
Figure 18: Stopping drug treatment
Some drugs are eliminated by zero-order elimination process. This means that the same amount of drug is eliminated per period of time. For example, 100 mg is eliminated per day, regardless of whether the total amount in the body is 600 mg or 20 grams. Such drugs do not have a half-life. This also means that the Cp/time curve never levels off to a certain maximum: the plasma concentration can rise forever if more of the drug is administered than the body can eliminate. To maintain a steady state you will have to administer exactly the amount that the body eliminates. The dosage of drugs in this category requires great care because of the increased risk of accumulation. Fortunately only a few such drugs exist. Examples are phenytoin, dicoumarol and probenicid. Acetylsalicylic acid in high dosage (grams per day) also behaves like this. And so does alcohol!