*2.4. Binding A*ffi*nity*

Binding affinity to an enzyme is measured by the *Km*, i.e., the concentration at which 50% of the maximum metabolic reaction (*Vmax*) occurs; the lower the *Km*, the greater the affinity. The intrinsic clearance measures the ability of an organ to clear unbound drug when there are no limitations to blood flow and binding considerations. The intrinsic clearance (*CLint)* of a substrate is defined by:

$$CL\_{int} = \frac{V \text{max}}{(Km + [S])}$$

where [*S*] is the substrate concentration. In most clinical situations, liver enzymes are rarely saturated so that, generally, the substrate concentration is much smaller than the *Km* and the equation can be simplified to:

$$CL\text{ }int\text{ }\approx\frac{Vm\text{ax}}{Km}$$

The binding affinity of a substrate can be modified by the presence of other molecules (in many drug–drug interaction situations, the *Km* is increased for the victim drug such that its *CLint* is decreased).
