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Effects of administration of estrogen or diphenylhydantoin on the kinetics of diphenylhydantoin in man.

The rate of disappearance of 131I-diphenylhydantoin (131I-DPH) from plasma and its hepatic uptake were studied during a control period and after estrogen administration in ten normal human subjects. Four subjects were given DPH and were studied in the same fashion as the estrogen-treated group. After intravenous injection of a tracer dose of 131I-DPH (period of study: 30-150 min after 131I-DPH administration), the estrogen-treated group showed an increase in the plasma half-time, a decrease in the fractional turnover rate, and a decrease in the distribution space of 131I-DPH in comparison with control. The hepatic uptake was decreased in comparison with the control, which may be explained by an increase in the binding capacity of thyroxine-binding globulin (TBG) induced by estrogens. An increase in the distribution space of 131I-DPH was observed in subjects treated with diphenylhydantoin. Consequently, the clearance rate was increased. No change in half-time or in turnover rate was observed. The hepatic uptake in the DPH-treated group was increased in comparison with control. This may be explained by a displacement of 131I-DPH by DPH from the binding sites of TBG. This study showed, therefore, that changes in the binding capacity of TBG are associated with alterations in the peripheral metabolism of 131I-DPH in man.