Extent of Urinary Excretion of p-Hydroxyphenytoin in Healthy Subjects Given Phenytoin

Abstract

Urinary excretion of p-hydroxyphenytoin and its glucuronide conjugate was measured in 8 healthy young adults in a comparative bioavailability study of oral sodium phenytoin (.apprx. 5 mg/kg/dose). Among these subjects the percentage of the phenytoin dose converted to p-hydroxyphenytoin and appearing in urine was relatively similar (mean 79%, range 67-88%). The great majority of the p-hydroxyphenytoin appeared in urine as conjugates; only 1.4-3.4% of the excreted p-hydroxyphenytoin was in the form of unconjugated metabolite. The proportion of a single phenytoin dose excreted in urine as p-hydroxyphenytoin or its conjugate increased from 1st dose (mean .+-. SD) 74.9 .+-. 4.6% to the 2nd dose, given 2 wk later 79.3 .+-. 4.6% (P < 0.05). Autoinduction of phenytoin metabolism may occur after relatively brief exposure to the drug.