Interaction of diphenylhydantoin (DPH) and tolbutamide in man

The influence of tolbutamide administration on the plasma concentrations of diphenylhydantoin (DPH) was investigated in seventeen long-stay patients with epilepsy. Tolbutamide, 0.5 g 2-3x daily, considerably increased the proportion of non-protein-bound DPH in plasma (mean: 44.6% of control values). The increase was transient, unlike the decrease found in total plasma DPH-concentration (approx. 10% of control values). In vitro experiments confirmed that the interaction between DPH and tolbutamide was due to displacement of DPH from plasma proteins. Some factors that limit the capacity to metabolise DPH in the liver are discussed; they may increase the risk of DPH-intoxication in patients who take sulphonyl-ureas.