Effectiveness of prednisolone during phenytoin therapy.

The effects of diphenylhydantoin (DPH) on the clearance of prednisolone from plasma, its bioavailability, and its biologic effectiveness were studied in 5 persons before and after daily DPH therapy for more than 3 wek. DPH decreased the mean half-time of disappearance of prednisolone from plasma by 45% and increased its metabolic clearance rate by an average of 77%. The gastrointestinal absorption of prednisolone and its first-pass clearance through splanchnic tissues were not significantly altered by DPH. The mean oral midnight dose of prednisolone required to suppress the 8 A.M. plasma level of cortisol to 5 microgram/dl was doubled following treatment of DPH. The increment in dose of prednisolone varied from 58% to 260% in the five individuals.