Comparative studies on the distribution and metabolic fate of diphenylhydantoin and 3-ethoxycarbonyldiphenylhydantoin (P-6127) after chronic administrations to dogs and cats.

The oral administration of 100 mg/kg/day of DPH or P-6127 to dogs and cats for more than 1 year resulted in preferential accumulations of the drugs in the superior and inferior colliculus, amygdala, and hippocampus compared to 16 other cerebral areas examined without any manifestation of neurotoxicity. The relative brain to blood levels of DPH in the animals were higher than those of epileptic patients on a maintenance dose. Both drugs were found concentrated in the pituitary and adrenal; P-6127 less so than DPH. This may be the cause of the infrequent gingival hyperplasia or hirsutism. DPH was metabolized to the pharmacologically inactive HPPH and a trace of inactive DPHA was found in the chronically treated animals. The ethoxycarbonyl group of P-6127 was split off to form DPH. The brain/blood and brain/cerebrospinal fluid concentration ratios were higher for P-6127 than for DPH. This may explain the greater anticonvulsant activity of P-6127 in the animals. [ABSTRACT FROM AUTHOR]