Diphenylhydantoin potency and plasma protein binding.

Rats were given diphenylhydantoin (DPH) orally, and its potency in protecting against maximal electroshock seizures was determined. The effect of an intravenous dose of 100 mg of phenylbutazone per kg 1 hour before testing on the potency and on the total and unbound plasma concentration of DPH was then measured. Phenylbutazone treatment increased the potency of DPH in terms of dose and total drug concentration but did not affect the potency of unbound DPH. The anticonvulsant action of DPH depends upon the concentration of unbound drug in plasma and not upon total plasma concentration nor upon dose.