Pharmacokinetics of antiepileptic drugs

The rational use of antiepileptic drugs requires the consideration of their pharmacokinetics, which may be influenced by the physiological and pathological factors. Pharmacokinetic interactions between antiepileptic drugs may lead to considerable fluctuation in plasma drug concentration, and monotherapy is often preferable. The absorption of phenytoin depends on pharmaceutical formulation. Phenytoin is highly bound to plasma proteins, thus the changes in the unbound fraction are of clinical significance. The saturation kinetics of its metabolism and drug interactions have further consequences. Carbamazepine is well absorbed and largely metabolized. Due to the autoinduction its half-life shortens in chronic administration. Valproate is highly, but variably bound to plasma proteins. It is eliminated mainly by metabolism. Due to the long half-life of phenobarbital its plasma concentrations change slowly, and time to the steady-state may be up to 30 days, if no loading dose is given. Primidone is partly metabolized to phenobarbital, and at steady-state plasma concentration of phenobarbital often exceeds that of primidone. Diazepam, clonazepam and nitrazepam are largely bound to plasma proteins and extensively metabolized with the half-lives of 20 to 60 hours.