02.05.3 First and Zero Order Kinetics

Graphs of plasma levels against time, can also tell us about the kinetics of the metabolism of the drug (Figure 2.11).

Figure 2.11 Metabolism and Kinetics (Copyright QUT, Sheila Doggrell)

With most drugs, there is a rapid fall in drug levels, as most drugs are readily metabolised, and there is an excess of enzyme available for the metabolism.  Thus, the enzyme never becomes saturated with drug.  This is known as first order kinetics (top, Figure 2.11).  In first order kinetics, increasing the concentration of the drug increases the metabolism of the drug.  First order kinetics is also observed with drugs that are eliminated unchanged.

With some drugs there is a limited amount of enzyme available to metabolise the drug, and when that limit is reached, metabolism occurs at a constant rate.  Thus, the enzyme becomes saturated with drug.  This is known as zero order kinetics, and is seen as a straight line on the graph (bottom, Figure 2.11).  In zero order kinetics, increasing the concentration of drug above a certain point does not increase the rate of metabolism.  The best known example of zero order kinetics is alcohol.  There are no notable examples of therapeutic drugs that have saturable metabolism and zero order kinetics.  However, some therapeutic drugs taken in excess can have saturable kinetics.  Examples include aspirin and the anti-epileptic drug phenytoin.