STIMULATORY EFFECT OF PHENOBARBITAL ON THE METABOLISM OF DIPHENYLHYDANTOIN

¹ The Wellcome Research Laboratories, Burroughs Wellconme & Co. (U.S.A.) Inc., Tuckahoe, New York, and The Department of Pharmacology, Albert Einstein College of Medicine, Bronz, New York

Pretreatment of dogs with phenobarbital or phetharbital increases markedly the disappearance of an intravenous dose of diphenylhydantoin. This observation is correlated with the elimination of the protective effects of diphenylhydantoin on maximal electroshock in mice that have been pretreated with phenobarbital, phetharbital or chlorcyclizine. In addition to the stimulatory effect of these drugs on diphenylhydantoin metabolism, they also stimulate the metabolism of phenylbutazone in the dog. Data are presented showing that phenylbutazone metabolism in the dog is stimulated markedly, not only by phenobarbital, phetharbital and chlorcyclizine, but by the chronic administration of phenylbutazone itself.