Therapeutic Drug Monitoring in Epilepsy

This review focuses on a clinical evaluation of drug monitoring in the therapy of epilepsy by antiepileptic drugs, especially phenytoin. Monitoring the blood levels of antiepileptic drugs has increased the efficacy and safety of drug therapy in epilepsy. However, in such monitoring, frequent determinations of the blood level of the drugs and careful evaluation of the individual differences in the pharmacokinetic parameters concerning absorption, distribution, metabolism and excretion of the drug are necessary. Most of the antiepileptic drugs are present in plasma, partly bound to protein and partly in the free (protein unbound) form. Both the clinical effect and intoxication induced by antiepileptic drugs are better correlated with the concentration of the free form rather than the total concentration of the drug in plasma. The determination of plasma, that is, the level of free form antiepileptic drugs, however, requires a large amount of blood and complicated time-consuming procedures. We described the use of saliva and tears to estimate rapidly, conveniently and noninvasively the concentration of the free form. We also discussed the essential need for reexamination of the "therapeutic range"of antiepileptic drugs, since the " therapeutic range" depends on the severity of the epilepsy, and since, in many cases of epilepsy, especially in " mild epilepsy," a lower level of the "therapeutic range"is sufficient to achieve complete seizure control