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Enantioselectivity of 4‐hydroxylation in extensive and poor metabolizers of debrisoquine.
Author(s) -
Eichelbaum M,
Bertilsson L,
Kupfer A,
Steiner E,
Meese CO
Publication year - 1988
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.1365-2125.1988.tb03335.x
Subject(s) - hydroxylation , debrisoquine , enantiomer , stereochemistry , chemistry , absolute configuration , metabolism , biochemistry , enzyme , cytochrome p450 , cyp2d6
Debrisoquine (DQ) has no chiral centre, but hydroxylation in position 4 leads to formation of an asymmetric carbon centre with two possible enantiomers, their absolute configuration being R(‐) and S(+)‐4‐ hydroxydebrisoquine (4‐OHDQ). Since the absolute stereochemistry of the 4‐hydroxylation of DQ in man is unknown, the enantioselectivity of this process was studied in panels of extensive (EM) and poor metabolizers (PM) of DQ. In EM subjects 4‐hydroxylation of DQ leads almost exclusively to the formation of S(+)‐4‐OHDQ. In contrast, PM subjects were not only characterized by a decreased total 4‐OHDQ formation but also a marked loss of enantioselectivity in product formation. Between 5 to 36% of total 4‐OHDQ was excreted as R(‐)‐4‐OHDQ.