THE HYDROXYLATION OF OMEPRAZOLE CORRELATES WITH S-MEPHENYTOIN METABOLISM - A POPULATION STUDY
THE HYDROXYLATION OF OMEPRAZOLE CORRELATES WITH S-MEPHENYTOIN METABOLISM - A POPULATION STUDY
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DOI：
10.1016/0009-9236(95)90229-5
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发表时间：
1995-06-01
影响因子：
6.7
通讯作者：
FLOCKHART, DA
中科院分区：
文献类型：
--
作者：
BALIAN, JD;SUKHOVA, N;FLOCKHART, DA
We compared omeprazole and mephenytoin as probes for the CYP2C19 metabolic polymorphism, Single oral doses of omeprazole (20 mg) or mephenytoin (100 mg) were administered at least 1 week apart to 167 healthy volunteers, Mephenytoin metabolism was measured using the amount of 4'-hydroxymephenytoin and the S/R ratio of mephenytoin in an 8-hour urine collection, Omeprazole hydroxylation was measured using the ratio of omeprazole to 5'-hydroxyomeprazole in serum 2 hours after dosing, All three methods separated poor- or extensive-metabolizer phenotypes with complete concordance, Omeprazole hydroxylation correlated with the S/R ratio of mephenytoin in extensive metabolizers (r(2) = 0.681; P < 0.001), Genotyping tests showed that six poor metabolizers of omeprazole were homozygous for a single base pair mutation in exon 5 of CYP2C19. These results support the hypothesis that omeprazole 5'-hydroxylation cosegregates with the CYP2C19 metabolic polymorphism.
