For many drug  there is a range of plasma concentrations that is associated with a clinical improvement in the majority of patients. Plasma concentration of drugs are described as subtherapeutic and toxic, respectively. Plasma concentration in the high therapeutic range may be considered potentially toxic.

The therapeutic plasma concentration is not a marginal range that guarantees successful treatment without adverse effect. Some patient require only a low plasma concentration, presumably because of differences in disease severity, tissue sensitivity, or pathophysiology. A low therapeutic or even subtherapeutic concentration may be adequate for their management. This level usually cannot be predicted in advance.

Adverse reaction may occur within the so called therapeutic concentration range. They may represent normal biological variation, enhanced sensitivity, idiosyncrasy, altered body binding, or variation in the “milieu interieure”, which may be superficially characterized by electrolyte disturbance. There may be summation or synergy with other medications. The measurement of drug concentration may be inaccurate, or the sample may be taken at an inappropriate time. The methodology may be disturbed, for example, by hemolysis, bile pigmentation, and the presence of other drug or interfering metabolites. Laboratory errors, both human and mechanical, may also occur.

When dosage or plasma concentration and response are not compatible by normal standards, pharmacodynamic, pharmacokinetic, or analytical interference should be considered. Many important interactions between drugs and disease have been exposed in this way.  (doc r3nd5an)