Hadidi H F, Irshaid Y M, Woosley R L, Idle J R, Flockhart D A
Department of Pharmacology, Faculty of Medicine, Jordan University of Science and Technology, Irbid.
Clin Pharmacol Ther. 1995 Nov;58(5):542-7. doi: 10.1016/0009-9236(95)90174-4.
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.
