Therapeutic drug monitoring--antiepileptic drugs

Abstract

Aims: To provide a brief critical review of the basis and contemporary practice of monitoring the concentrations of antiepileptic drugs in biological fluids.

Methods: The review is based on literature data and observations from clinical practice.

Results: As experience has accumulated, monitoring of antiepileptic drug concentrations has come to be applied mainly to certain of the drugs when present in whole plasma. For these drugs there is a reasonably established relationship between drug concentrations and biological effects, but attention still needs to be paid to issues such as the timing of the measurements in relation to drug intake, the presence or absence of steady-state conditions, the presence in plasma of active metabolites and possible nonlinear pharmacokinetics of particular agents e.g. phenytoin.

Conclusions: Plasma antiepileptic drug concentration monitoring is coming to be used in a more thoughtful and critical manner. Lack of adequate knowledge of matters such as the relationship between the plasma concentrations and antiepileptic and toxic effects of the drugs, not only the newer, but also the longer established ones, in particular clinical situations, remains more important than deficiencies in analytical methodology in limiting the clinical usefulness of antiepileptic drug concentration monitoring.

Figure 1

Cumulative percentages of patients treated with carbamazepine and whose seizures were fully controlled for at least 1 year plotted (spline fits) against plasma carbamazepine concentration for 20 patients with generalized epilepsy (continuous line) and 52 patients with partial epilepsy (broken line) who received the drug as monotherapy (upper pair of curves, solid symbols), and for 78 patients with generalized epilepsy and 118 patients with partial epilepsy who received the drug as part of an antiepileptic drug combination (lower pair of curves, open symbols). After ‘43’, reproduced with permission.