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. 1988 Apr;25(4):505–508. doi: 10.1111/j.1365-2125.1988.tb03335.x

Enantioselectivity of 4-hydroxylation in extensive and poor metabolizers of debrisoquine.

M Eichelbaum 1, L Bertilsson 1, A Küpfer 1, E Steiner 1, C O Meese 1
PMCID: PMC1387813  PMID: 3382592

Abstract

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.

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Selected References

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