Effective prescribing of anticonvulsants requires foreknowledge of baseline pharmacokinetic data. Little such information is available about the hydantoins other than phenytoin, although one of them, mephenytoin, is widely used. Useful pharmacokinetic data should be derived from patients already exposed to anticonvulsants to reflect the induction of hepatic oxidative enzymes. Single-dose studies of mephenytoin (Mesantoin) and ethotoin (Peganone) were performed in adult inpatients on stable regimens of other anticonvulsants. Five patients received rnephenytoin, 7 mg per kilogram of body weight. Serial blood sampling was performed rigorously. The time to peak concentration (TmaX) for rnephenytoin was 1 hour, with a half-life (T112) of 7 hours; the TI,, of its metabolite, 5-ethyl-5-phenylhydantion, was 96 hours. Ethotoin administration was 25 mg per kilogram in 5 patients. Ethotoin T,,, was 2 hours, with a T,,, of 5 hours. Saliva accurately represented the unbound fraction for all three agents. Mean salivary levels (as percentage of total levels) were 61% for mephenytoin, 7396 for its metabolite, and 54% for From the Epilepsy Center,