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Lack of relationship between glibenclamide metabolism and debrisoquine or mephenytoin hydroxylation phenotypes.
Author(s) -
DahlPuustinen ML,
Alm C,
Bertilsson L,
Christenson I,
Ostman J,
Thunberg E,
Wikstrom I
Publication year - 1990
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/j.1365-2125.1990.tb03800.x
Subject(s) - mephenytoin , debrisoquine , glibenclamide , pharmacokinetics , urine , hydroxylation , pharmacology , cyp2c19 , excretion , chemistry , pharmacogenetics , medicine , metabolism , endocrinology , urinary system , biology , cyp2d6 , biochemistry , cytochrome p450 , diabetes mellitus , genotype , enzyme , gene
The pharmacokinetics of a single oral dose of 1.75 mg glibenclamide were studied in 15 healthy Caucasians including five poor metabolisers of debrisoquine and five poor metabolisers of S‐mephenytoin. Plasma glibenclamide concentrations and the urinary concentrations of trans‐4‐ and cis‐3‐hydroxyglibenclamide were analyzed by h.p.l.c. Thirty‐six +/− 6% (mean +/− s.d., n = 15) of the given dose of glibenclamide was excreted in 48 h urine as hydroxylated metabolites, 27 +/− 4% as trans‐ 4‐hydroxyglibenclamide and 8 +/− 2% as cis‐3‐hydroxyglibenclamide. There were no differences in the plasma pharmacokinetics of glibenclamide or in the urinary excretion of the metabolites between poor and extensive metabolisers of debrisoquine, neither between the two mephenytoin hydroxylator phenotypes. The study thus indicates that the disposition of glibenclamide is not influenced by these two independent polymorphisms of drug oxidation.