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Pharmacokinetics of antiepileptic drugs

From the Departments of Neurology and Pharmacology, Boston University School of Medicine, and the Neurology Service, Boston Department of Veterans Affairs Medical Center, Boston, MA.

Address correspondence and reprint requests to Dr. Thomas R. Browne, Neurology Service (127), DVA Medical Center, 150 S. Huntington Avenue, Boston, MA 02130.

Abstract.

Enzymatic biotransformation is the principal determinant of the pharmacokinetic properties of most antiepileptic drugs (AEDs), although some agents are excreted by the kidneys predominantly as unchanged drug. Most AEDs exhibit linear enzyme kinetics, in which changes in daily dose lead to proportional changes in serum concentration if clearance remains constant. There are several important applications of pharmacokinetics in clinical practice. Established therapeutic ranges help guide drug administration to achieve serum concentrations that control seizures without causing intolerable toxicity. Determination of the elimination half-life may provide a basis for selecting a dosing interval and predicting the time to steady-state concentration. However, the traditional concept of administering a drug at intervals equal to one elimination half-life does not apply to some drugs. With vigabatrin, the half-life of biologic activity greatly exceeds the half-life of elimination. In situations in which it is desirable to achieve a steady-state serum concentrations immediately, a loading dose can be calculated from a drug's volume of distribution and its desired serum concentration. Many AEDs have the potential to be involved in pharmacokinetic drug interactions when they are co-administered with other AEDs or other medications. These interactions usually involve changes in the rate of biotransformation or in the protein binding of one or both co-administered drugs.