A Review with a Case History on the Effect of Renal Failure

Although the majority of individuals medicated with diphenylhydantoin require doses in the range of 4–6 mg/kg/day (300–400 mg/day), there are many people who are known to deviate from this average in their requirements. Other persons may be stablized on a given dose of diphenylhydantoin, yet develop toxic signs or demonstrate lack of therapeutic effect at a later time. This paper reviews basic pharmacokinetics and elimination data for diphenylhydantoin, as well as the various parameters recognized as influencing diphenylhydantoin dosing requirements. A case history is presented¹ to illustrate the possible effects of renal failure and how one individual's requirements changed as his clinical status changed.

Among the physiological factors considered are liver function, renal function, genetic influences on metabolic disposition, and alterations that occur in serum protein binding of diphenylhydantoin. Physical characteristics that are considered include variability in formulation of various solid oral dosage forms, hazards of oral suspensions of diphenylhydantoin, efficacy of intramuscular injections, and failure of diphenylhydantoin to obey first order elimination kinetics. Finally, interaction of other drug products with diphenylhydantoin is discussed and summarized.