Mephenytoin, Ethotoin, & Phenacemide

MEPHENYTOIN, ETHOTOIN, & PHENACEMIDE

Many congeners of phenytoin have been synthesized, but only three have been marketed in the USA, and one of these (phenacemide) has been withdrawn. The other two congeners, mephenytoin and ethotoin, like phenytoin, appear to be most effective against generalized tonic-clonic seizures and partial seizures. No well-controlled clinical trials have documented their effectiveness. The incidence of severe reactions such as dermati-tis, agranulocytosis, or hepatitis is higher for mephenytoin than for phenytoin.Ethotoin may be recommended for patients who are hyper-sensitive to phenytoin, but larger doses are required. The adverse effects and toxicity are generally less severe than those associated with phenytoin, but the drug appears to be less effective.Both ethotoin and mephenytoin share with phenytoin the property of saturable metabolism within the therapeutic dosage range. Careful monitoring of the patient during dosage alterations with either drug is essential. Mephenytoin is metabolized to 5,5-ethylphenylhydantoin via demethylation. This metabolite, nirvanol, contributes most of the antiseizure activity of mepheny-toin. Both mephenytoin and nirvanol are hydroxylated and undergo subsequent conjugation and excretion. Therapeutic levels for mephenytoin range from 5 to 16 mcg/mL, and levels above 20 mcg/mL are considered toxic.Therapeutic blood levels of nirvanol are between 25 and 40 mcg/mL. A therapeutic range for ethotoin has not been established.