Quinidine inhibition of debrisoquine S(+)-4- and 7-hydroxylations in Chinese of different CYP2D6 genotypes.

  title={Quinidine inhibition of debrisoquine S(+)-4- and 7-hydroxylations in Chinese of different CYP2D6 genotypes.},
  author={L. Bertilsson and C. Meese and Q. Yue and M. Dahl and M. Ingelman-Sundberg and I. Johansson and J. S{\"a}we and M. Eichelbaum},
  volume={3 2},
Pronounced differences in the CYP2D6 gene between Chinese and Caucasians have previously been described. There was a low frequency of detrimental mutations in the Chinese CYP2D6 gene causing the poor metabolizer (PM) phenotype. In contrast to Caucasians where the Xba I 44 kb allele is almost always associated with the PM phenotype, Chinese with the 44/44 kb RFLP pattern are extensive metabolizers (EM). In order to evaluate whether the debrisoquine hydroxylation seen in subjects with this… Expand
Inhibition of debrisoquine hydroxylation with quinidine in subjects with three or more functional CYP2D6 genes.
Normalizing the metabolic capacity of CYP2D6, by giving a low dose of quinidine, may solve the problem of 'treatment resistance' caused by ultrarapid metabolism. Expand
Regioselective hydroxylation of debrisoquine by cytochrome P4502D6: implications for active site modelling
The precise regioselective hydroxylation of debrisoquine by CYP2D6 was determined, demonstrating the need to consider the mechanism of oxidation as well as the spatial orientation of the substrate in the development of a predictive model of the active site of CYP1D6. Expand
Different effects of inhibitors on the O - and N -demethylation of codeine in human liver microsomes
  • Q. Yue, J. Säwe
  • Chemistry, Medicine
  • European Journal of Clinical Pharmacology
  • 1997
There was a good correspondence between the capacity of drugs to inhibit the O- and N-demethylation of codeine in human liver microsomes and their apparent metabolism by CYP2D6 or CYP3A4, respectively in vivo in man, suggesting that this in vitro inhibition test may be a useful screen for drugs which interact with these two important drug-metabolising enzymes. Expand
Effect of metabolic blockade on the psychoactive effects of dextromethorphan
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Improved high-performance liquid chromatographic determination of debrisoquine and 4-hydroxydebrisoquine in human urine following direct injection.
  • R. Frye, R. Branch
  • Chemistry, Medicine
  • Journal of chromatography. B, Biomedical applications
  • 1996
A sensitive and specific reversed-phase high-performance liquid chromatographic assay was developed that is suitable of pharmacogenetic studies utilizing debrisoquine and 4-hydroxydebrisoquine in urine and accuracy was within 12%. Expand
Impact of metabolizing enzymes on drug response of endocrine therapy in breast cancer
The authors will discuss the current evidence on the most important metabolizing enzymes in endocrine therapy, with a special focus on CYP2D6 and its role in tamoxifen metabolism. Expand