Comparative drug elimination in man — Diphenylhydantoin and amobarbital

Summary

The concentration of 5,5-diphenylhydantoin (DPH) in serum was determined at selected time intervals in seven healthy male volunteers starting 10 h after an oral dose of 400 mg sodium DPH was given. The data were analyzed according to a one-compartment model assuming first-order kinetics. The mean serum half-life was 19.28 h±5.87 (SD). A positive correlation coefficient (r=0.84, p<0.05) was found between the serum DPH half-life and the serum amobarbital half-life in the seven subjects. The urinary levels of free plus conjugated 5-(p-hydroxyphenyl)-5-phenylhydantoin were determined for 12 h periods over a minimum of two days following the 400 mg oral dose of sodium DPH. Subjects with a short DPH half-life tended to excrete in urine a greater amount ofp-HPPH as compared to subjects with a long DPH half-life. In the case of one subject, the urinary excretion ofp-HPPH plateaued five days after DPH administration and the apparent elimination half-life determined from thep-HPPH urinary excretion data was 19.16 h as compared to the value of 19.53 h calculated from the DPH serum levels.