Antiepileptic drugs: pharmacokinetic and clinical aspects

Serum level monitoring of antiepileptic drugs is important for an optimal drug therapy since relationships between serum levels and therapeutic and toxic effects have been clearly established for several drugs. Routine serum level monitoring based on pharmacokinetic and clinical knowledge has improved the treatment of epileptic patients. For routine determination of antiepileptic drugs, homogenous enzyme immunoassays offer several advantages over more complex techniques such as GLC and HPLC. Because of the speed of the analysis and the small sample volume, EMIT is the method of choice in many laboratories. A 50-microliter sample is sufficient for a single determination of up to five drugs. To ensure reliable results, quality control schemes are necessary regardless of the analytical technique utilized for drug quantitation. Routine monitoring of serum levels is especially important since drug bioavailability, as well as the rate of drug metabolism and excretion, varies widely among patients. Serum levels are also influenced by comedication. Changes in protein binding may also be of clinical importance under special circumstances. Active metabolites may contribute to the clinical effect of a drug. Correct dose frequency and standardized blood sampling time, preferably before the first morning drug dose, are also important factors for establishing optimal therapeutic regimens for a given patient. The serum levels of antiepileptic drugs should be determined when drug therapy is initiated, after dosage adjustments, in case of therapy failure, after addition of drugs which may cause drug interactions, when clinical signs of side effects or drug intoxication occur, and as a routine monitoring for patient compliance. Serum levels should be monitored if any change occurs in a patient's normal pharmacological state.