The Role of Therapeutic Drug Monitoring in Patient Care*

The dose-response relationship for antiepileptic drugs (AEDs) varies enormously between and within individual patients. Variations are caused by a variety of factors, including poor dose-concentration correlations, metabolic variations due to age, physiologic status, disease, and concomitant medications. Consequently, there is a rationale for establishing an individualized reference concentration for new epilepsy patients, as well as for those patients who are expected to undergo significant metabolic changes (eg, puberty, pregnancy). There is also considerable benefit to be derived from intensive therapeutic drug monitoring for certain defined groups of patients. Depending on the type of AED used and the circumstances of use, consideration may need to be given to monitoring free fractions, metabolites, and peak or trough concentrations. (Adv Stud Med. 2004;4(7C):S599-S606) T he primary goal of antiepileptic drug (AED) therapy is 100% seizure control. The path to this ideal lies somewhere between the peaks of toxicity and unacceptable adverse effects and the valley of low serum levels with breakthrough seizures. Even a low rate of incidence of seizures can have devastating consequences with regard to the patient’s lifestyle, whereas toxic effects of medication can occur gradually and insidiously. To add to the difficulty of finding the correct balance, the correlations between dosage and efficacy and between dosage and toxicity are not reliable. Variability exists among individuals in absorption rates, body weight, drug distribution, protein binding, hepatic metabolism, and renal excretion. This picture can be further complicated by poor compliance. There may also be changes in pharmacokinetics within an individual due to changes in age, health, pregnancy, or concomitant medications. Therapeutic drug monitoring (TDM) allows the clinician to bypass the uncertainty of AED doseresponse relationships and use the better correlations that exist between drug concentration and both efficacy and toxicity. TDM is most useful if there is an established correlation between drug concentration, therapeutic effect, and toxic side effects and if the therapeutic window is narrow. TDM is not, however, universally required or even universally desirable. This article describes some of the circumstances in which TDM can be helpful to the clinician in evaluating and titrating AED dosage. It also examines some of the contraindications for TDM. PROCEEDINGS