Phenytoin hydroxylation in a healthy Caucasian population: bimodal distribution of hydroxyphenytoin urinary excretion.
The phenytoin hydroxylation index was studied in 122 unrelated Caucasian volunteers. Following a 100 mg oral dose of phenytoin, phenytoin and hydroxyphenytoin were measured in urine from 0-32 hr after administration. As phenytoin was not found in all urine collections, a phenytoin hydroxylation index was expressed as follows: Phenytoin hydroxylation index = amount of phenytoin administered/0-32 hr urinary output of hydroxyphenytoin. Phenytoin hydroxylation index values appear to be bimodally distributed, 92% of the population showing a mean (+/- S.E.M.) value of 0.639 +/- 0.099 and 8% a mean (+/- S.E.M.) value of 1.001 +/- 0.180 (log10 values). These results are in favour of the existence of a phenytoin genetic polymorphism. Since misuse of urinary metabolite excretion data in drug metabolism studies is a well-known phenomenon, our data emphasize the need for future population studies on phenytoin pharmacokinetics as well as on CYP2C9 genotyping before concluding about existence of a phenytoin genetic polymorphism.
Horsmans
Y
Y
Laboratory of Pharmacotherapeutics, Catholic University of Louvain, Bruxelles, Belgium.
Van den Berge
V
V
Bouckaert
A
A
Desager
J P
JP
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D001189:Aryl Hydrocarbon Hydroxylases; D015331:Cohort Studies; D065729:Cytochrome P-450 CYP2C9; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D005260:Female; D006801:Humans; D006900:Hydroxylation; D008019:Life Style; D008297:Male; D010672:Phenytoin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics* / Q000652:urine; D011110:Polymorphism, Genetic; D039181:Steroid 16-alpha-Hydroxylase; D013250:Steroid Hydroxylases / Q000235:genetics; D044465:White People / Q000235:genetics
C001419:hydroxyphenytoin; D010672:Phenytoin; D003577:Cytochrome P-450 Enzyme System; D013250:Steroid Hydroxylases; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; D039181:Steroid 16-alpha-Hydroxylase