Figure XX-4 Plot of Salicylate Amount in the Body Versus Time. Similar t1/2 at Lower Concentrations Only
Another drug with saturable elimination kinetics is aspirin or maybe more correctly salicylate. In the case of aspirin or salicylate poisoning the elimination maybe much slower than expected because of Michaelis-Menten kinetics as shown in Figure XX-4
Diagram XX-2 Scheme for Aspirin/Salicylate Elimination
In the case of aspirin we have parallel first order process with the Michaelis-Menten kinetics. Therefore as dose increases proportionally more drug would be removed by the first order processes rather than the saturable one. This is shown in the figure below (Figure XX-5).
Figure XX-5 Plot of Apparent t1/2 Versus log(DOSE)
The phenomena of non-linear pharmacokinetics is of great importance in multiple dose therapy in which more significant changes in the plateau levels are produced by the accumulation of drug in the body than can be expected in single dose studies. This accumulation will result in toxic responses especially when the therapeutic index of the drug is low.
Copyright 2001 David W.A. Bourne