Effectiveness of prednisolone during phenytoin therapy

Clin Pharmacol Ther. 1977 Dec;22(6):912-6. doi: 10.1002/cpt1977226912.


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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Biological Availability
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Hydrocortisone / blood
  • Kinetics
  • Male
  • Phenytoin / blood
  • Phenytoin / pharmacology*
  • Prednisolone / antagonists & inhibitors*
  • Prednisolone / metabolism


  • Phenytoin
  • Prednisolone
  • Hydrocortisone