S-mephenytoin hydroxylation phenotypes in a Jordanian population.
We tested the ability of 194 unrelated, healthy Jordanian volunteers to metabolize S-mephenytoin. Mephenytoin (100 mg) was coadministered with debrisoquin (10 mg) orally and urine was collected for 8 hours. Mephenytoin metabolism was tested according to three measures: the amount of 4-hydroxymephenytoin, the S/R enantiomeric ratio, and the presence of a polar, acid-labile metabolite in urine collected for 8 hours after the dose. The S/R ratio and the presence of the acid-labile metabolite were determined in the urine of 16 patients who had low amounts of 4-hydroxymephenytoin (log hydroxylation index > or = 1). On examination of these three parameters of oxidation status, nine subjects were found to be poor metabolizers of mephenytoin by all three parameters. Thus 4.6% (95% confidence interval of 1.6% to 7.6%) of Jordanian subjects studied were poor metabolizers of mephenytoin. According to the Hardy-Weinberg Law, the frequency of the recessive autosomal gene controlling the poor metabolizer status of mephenytoin was predicted to be 0.215% (95% confidence interval of 0.146% to 0.283%). These results are on the same order of magnitude as those determined in European white populations and constitute the first report in Arab populations.
Hadidi
H F
HF
Department of Pharmacology, Faculty of Medicine, Jordan University of Science and Technology, Irbid.
Irshaid
Y M
YM
Woosley
R L
RL
Idle
J R
JR
Flockhart
D A
DA
D000293:Adolescent; D000328:Adult; D000927:Anticonvulsants / Q000378:metabolism*; D003647:Debrisoquin / Q000008:administration & dosage; D005260:Female; D005787:Gene Frequency; D006801:Humans; D006900:Hydroxylation; D007597:Jordan; D008297:Male; D008617:Mephenytoin / Q000031:analogs & derivatives / Q000378:metabolism* / Q000652:urine; D008660:Metabolism / Q000235:genetics; D008875:Middle Aged; D010641:Phenotype; D015995:Prevalence; D013565:Sympatholytics / Q000008:administration & dosage
D000927:Anticonvulsants; D013565:Sympatholytics; C025687:4-hydroxymephenytoin; D008617:Mephenytoin; D003647:Debrisoquin