Determination of optimal diphenylhydantoin dosage by monitoring serum concentrations

The efficacy of treatment with diphenylhydantoin (DPH) and serum DPH concentrations were compared in 20 patients with epilepsy or following brain surgery, before and after determination of the optimal individual dose. The dose was determined by a graphic analysis of the Michaelis-Menten kinetics of DPH in each patient. Before the trial, while on routine therapy (200-300 mg/day), subtherapeutic serum concentrations of DPH (<8 mcg/ml) were present in 18/20 patients, a potentially toxic level (>20 mcg/ml) in 1/20 and in only one patient were DPH concentrations in the therapeutic range found. Following dose individualization, DPH concentrations within the therapeutic range were achieved in all 20 patients, with considerable improvement in seizure control. Because of the nonlinear relationship between DPH dosage and serum concentrations, suboptimal treatment is common, as is potential toxicity following relatively small increments of the drug. Monitoring serum DPH concentrations affords a means of defining the saturation point of each patient - allowing dose optimalization without attendant toxicity.