PHENYTOIN HYDROXYLATION IN A HEALTHY CAUCASIAN POPULATION - BIMODAL DISTRIBUTION OF HYDROXYPHENYTOIN URINARY-EXCRETION

The phenytoin hydroxylation index was studied in 122 unrelated Caucasi an volunteers. Following a 100 mg oral dose of phenytoin, phenytoin an d hydroxyphenytoin were measured in urine from 0-32 hr after administr ation. As phenytoin was not found in all urine collections, a phenytoi n hydroxylation index was expressed as follows: Phenytoin hydroxylatio n index=amount of phenytoin administered/0-32 hr urinary output of hyd roxyphenytoin. Phenytoin hydroxylation index values appear to be bimod ally distributed, 92% of the population showing a mean (+/-S.E.M.) val ue of 0.639+/-0.099 and 8% a mean (+/-S.E.M.) value of 1.001+/-0.180 ( log(10) values). These results are in favour of the existence of a phe nytoin genetic polymorphism. Since misuse of urinary metabolite excret ion data in drug metabolism studies is a well-known phenomenon, our da ta emphazise the need for future population studies on phenytoin pharm acokinetics as well as on CYP2C9 genotyping before concluding about ex istence of a phenytoin genetic polymorphism.