S-Mephenytoin hydroxylation phenotypes in a Jordanian population
Hakam F. Hadidi, Yacoub M. Irshaid, Raymond L. Woosley, Jeffrey R. Idle, David A. Flockhart
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 ≥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.
Mephenytoin
Debrisoquin
Recessive Genes
Hadidi, H. F., Irshaid, Y. M., Woosley, R. L., Idle, J. R., & Flockhart, D. A. (1995). S-Mephenytoin hydroxylation phenotypes in a Jordanian population. Clinical Pharmacology and Therapeutics, 58(5), 542-547.
S-Mephenytoin hydroxylation phenotypes in a Jordanian population. / Hadidi, Hakam F.; Irshaid, Yacoub M.; Woosley, Raymond L.; Idle, Jeffrey R.; Flockhart, David A.
In: Clinical Pharmacology and Therapeutics, Vol. 58, No. 5, 11.1995, p. 542-547.
Hadidi, HF, Irshaid, YM, Woosley, RL, Idle, JR & Flockhart, DA 1995, 'S-Mephenytoin hydroxylation phenotypes in a Jordanian population', Clinical Pharmacology and Therapeutics, vol. 58, no. 5, pp. 542-547.
Hadidi HF, Irshaid YM, Woosley RL, Idle JR, Flockhart DA. S-Mephenytoin hydroxylation phenotypes in a Jordanian population. Clinical Pharmacology and Therapeutics. 1995 Nov;58(5):542-547.
Hadidi, Hakam F. ; Irshaid, Yacoub M. ; Woosley, Raymond L. ; Idle, Jeffrey R. ; Flockhart, David A. / S-Mephenytoin hydroxylation phenotypes in a Jordanian population. In: Clinical Pharmacology and Therapeutics. 1995 ; Vol. 58, No. 5. pp. 542-547.
@article{51855226b25b4b9ba03b84ad39b28a7f,
title = "S-Mephenytoin hydroxylation phenotypes in a Jordanian population",
abstract = "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 ≥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.",
author = "Hadidi, {Hakam F.} and Irshaid, {Yacoub M.} and Woosley, {Raymond L.} and Idle, {Jeffrey R.} and Flockhart, {David A.}",
journal = "Clinical Pharmacology and Therapeutics",
T1 - S-Mephenytoin hydroxylation phenotypes in a Jordanian population
AU - Hadidi, Hakam F.
AU - Irshaid, Yacoub M.
AU - Woosley, Raymond L.
AU - Idle, Jeffrey R.
AU - Flockhart, David A.
N2 - 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 ≥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.
AB - 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 ≥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.
JO - Clinical Pharmacology and Therapeutics
JF - Clinical Pharmacology and Therapeutics