The rate of decline of diphenylhydantoin in human plasma

Abstract

The rate of disappearance of diphenylhydantoin from plasma was studied in 70 healthy volunteers by giving them 100 mg. orally 3 times daily for 3 days and measuring the plasma diphenylhydantoin concentration for 4 consecutive days after the last dose of the drug. The mean plasma half‐life was 22.0 ± 9.0 hours and the difference between that of Negro and Caucasian males, 26.5 and 18.5 hours, respectively, was Significant. Dose dependency of the half‐life was demonstrated in 10 subjects studied. The decline in plasma diphenylhydantoin concentration in many subfects was not exponential and the disappearance of the drug from plasma was not always a first‐order process. The diphenylhydantoin half‐life in some subjects was shorter after long‐term administration than after short‐term administration of the drug. Saturation, autoinduction, or product inhibition, singly or in combination, of the drug‐metabolizing enzyme system are possible mechanisms involved in the dose dependency and nonexponential decline of plasma diphenylhydantoin concentration.