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Metabolic disposition of lansoprazole in relation to the S ‐mephenytoin 4′‐hydroxylation phenotype status
Author(s) -
Sohn DongRyul,
Kwon JunTack,
Kim HyungKee,
Ishizaki Takashi
Publication year - 1997
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/s0009-9236(97)90137-5
Subject(s) - lansoprazole , mephenytoin , cyp2c19 , pharmacology , chemistry , hydroxylation , urine , pharmacokinetics , cyp3a4 , oral administration , omeprazole , medicine , metabolism , biochemistry , cytochrome p450 , enzyme
Objective To assess the possible involvement of CYP2C19 in the metabolism of lansoprazole in vivo. Methods Sixteen male Korean subjects, who had been phenotyped as extensive metabolizers and poor metabolizers of S ‐mephenytoin 4′‐hydroxylation polymorphism ( n = 8 each) with racemic mephenytoin with use of the 8‐hour urine analysis of 4′‐hydroxymephenytoin, took an oral dose of 30 mg lansoprazole, and blood samples were collected up to 48 hours after dosing. Lansoprazole and its metabolites were measured by high‐performance liquid chromatography with ultraviolet detection. Results The mean lansoprazole area under the concentration‐time curve (AUC), elimination half‐life (t 1/2 ), and apparent oral clearance (CL oral ) were significantly ( p < 0.001) greater, longer, and lower, respectively, in the poor metabolizer than in the extensive metabolizer group. The mean values for the AUC of hydroxylansoprazole and AUC ratio of hydroxylansoprazole to lansoprazole were significantly ( p < 0.01 to p < 0.001) less in the poor metabolizer than in the extensive metabolizer group, whereas those for the AUC of lansoprazole sulfone and ratio of lansoprazole sulfone to lansoprazole were greater ( p < 0.001) in the former than in the latter group. In addition, the log 10 4′‐hydroxymephenytoin excreted in urine correlated significantly ( p < 0.01) with the CL oral of lansoprazole. Conclusions These results suggest that the hydroxylation of lansoprazole cosegregates with the genetically determined S ‐mephenytoin 4′‐hydroxylation (CYP2C19) polymorphism in the Korean subjects. Clinical Pharmacology & Therapeutics (1997) 61 , 574–582; doi:

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