Extent of urinary excretion of p-hydroxyphenytoin in healthy subjects given phenytoin

Urinary excretion of p-hydroxyphenytoin and its glucuronide conjugate was measured in eight healthy young adults in a comparative bioavailability study of oral sodium phenytoin (~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 /j-hydroxyphenytoin was in the form of unconjugated metabolite. The proportion of a single phenytoin dose excreted in urine as /?-hydroxyphenytoin or its conjugate increased from the first dose (mean ± SD) 74.9 ± 4.6% to the second dose, given 2 weeks later 79.3 ± 4.6% (p < 0.05). This finding suggests that autoinduction of phenytoin metabolism may occur after relatively brief exposure to the drug.