Metabolism of diphenylhydantoin (phenytoin) during pregnancy.

Plasma levels of diphenylhydantoin (DPH) and the 24 hour urinary excretion of both DPH and its major metabolite 5-(p-hydroxyphenyl)-phenylhydantoin (HPPH) were measured serially during pregnancy in a group of five unselected epileptic patients. Plasma DPH levels fell and on average were some 40 per cent lower at term than they had been in early pregnancy. With one exception, the patients were well controlled during pregnancy but two patients who regularly had plasma DPH levels below 10 microgram/ml both suffered seizures in the puerperium. There was no convincing change in the excretion of either DPH or HPPH which together accounted for less than half the administered dose. Gestational length exceeded 41 weeks in 4 of the 5 patients studied but all were delivered of normal healthy infants, of average birthweight, with no congenital defects or clotting disorders.