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KMID : 0616619980040010033
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Journal of Soonchunhyang Medical College
1998 Volume.4 No. 1 p.33 ~ p.41
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Utility of omeprazole as a probe drug for phenotyping of S-mephenytoin hydroxylation polymorphism
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Abstract
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Racemic mixture of mephenytoin has been used to measure the CYP2C19. However, mephenytoin is not available in Korea, and its sedative effect limits its use in Oriental population. The purpose of this study was to evaluate the usefulness of. omeprazole as a probe drug for S-mephenytoin polymorphism. Single oral doses of mephenytoin or omeprazole were administered at least 2 weeks apart to 123 and 93 healthy volunteers, respectively. The capacity of S-mephenytoin hydroxylation was measured using the amount of hydroxymephenytoin excreted in 8-hr urine after taking 100 mg of mephenytoin, and omeprazole hydroxylation activity was defined as logio [omeprazole/hydroxyomeprazole] determined in plasma collected 2 hr after taking a 20 mg of omeprazole. Both methods separated poor metabolizer (PM) or extensive metabolizer (EM) phenotypes of polymorphism with complete concordance. But, omeprazole hydroxylation index does not correlated well (rz = 0.108) with the logio % hydroxymephenytoin excreted in EMs. The PMs identified by the logio % hydroxymephenytoin excreted were also assigned as PMs of omeprazole with the antimode of 1.0. The results suggest that omeprazole appears to be a safe and convenient tool to identify the capacity of S-mephenytoin hydroxylation.
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