Quinidine and the identification of drugs whose elimination is impaired in subjects classified as poor metabolizers of debrisoquine.

@article{Speirs1986QuinidineAT,
  title={Quinidine and the identification of drugs whose elimination is impaired in subjects classified as poor metabolizers of debrisoquine.},
  author={C. Speirs and S. Murray and A. Boobis and C. E. Seddon and D. Davies},
  journal={British journal of clinical pharmacology},
  year={1986},
  volume={22 6},
  pages={
          739-43
        }
}
Quinidine and its diastereoisomer quinine were tested in vitro for their effect on the 4-hydroxylation of debrisoquine, the O-deethylation of phenacetin and the 1'-hydroxylation of bufuralol, by human liver microsomal samples; quinidine was studied for its effect on debrisoquine 4-hydroxylation in vivo. Quinidine was a potent inhibitor of the 4-hydroxylation of debrisoquine and the 1'-hydroxylation of bufuralol, with IC50 values of 0.7 and 0.2 microM, being around 100 times more potent in this… Expand
Comparative effects of the diastereoisomers, quinine and quinidine in producing phenocopy debrisoquine poor metabolisers (PMs) in healthy volunteers.
TLDR
It is concluded that quinidine, but not its diastereoisomer quinine, is a potent selective inhibitor of the in vivo oxidation of debrisoquine and can produce an artifactual PM phenocopy in persons who are phenotypically extensive metaboliser (EM) phenotype status. Expand
Quinidine inhibits the 7-hydroxylation of chlorpromazine in extensive metabolisers of debrisoquine
TLDR
The data suggest that CYP2D6 is involved in the metabolism of chlorpromazine to 7-hydroxychlorpromazine, however, genetic polymorphism in this metabolic process did not play a dominant role in accounting for the extremely large interindividual variations in plasma concentrations encountered with this drug. Expand
Quinidine but not quinine inhibits in man the oxidative metabolic routes of methoxyphenamine which involve debrisoquine 4-hydroxylase
TLDR
In the extensive metabolizer phenotype it was demonstrated in one study that enzyme inhibition of quinidine was selective in terms of the metabolic pathways inhibited as well as stereoselective with respect to the inhibitor. Expand
Genetically-determined interaction between propafenone and low dose quinidine: role of active metabolites in modulating net drug effect.
1. Quinidine is a potent inhibitor of the genetically-determined debrisoquine 4-hydroxylation. Oxidation reactions of several other drugs, including the 5-hydroxylation of the new antiarrhythmic drugExpand
The specificity of inhibition of debrisoquine 4-hydroxylase activity by quinidine and quinine in the rat is the inverse of that in man.
TLDR
The data in this paper are consistent with 4-hydroxylation of debrisoquine in both rat and human liver catalysed by a specific form of cytochrome P-450, and suggest that data on the specificity of this isoenzyme in the rat should be extrapolated to man with extreme caution. Expand
Selective in vivo inhibition by quinidine of methoxyphenamine oxidation in rat models of human debrisoquine polymorphism.
TLDR
A protocol involving substrate administration to Lewis strain rats with and without prior administration of quinidine could be developed as an attractive approach to screen substrates for metabolism in vivo by the debrisoquine/sparteine isozyme. Expand
4-Hydroxylation of debrisoquine by human CYP1A1 and its inhibition by quinidine and quinine.
TLDR
Findings have significant implications for the conduct of in vitro drug metabolism inhibition studies and underscore the fallacy of "specific chemical inhibitors" of a supergene family of enzymes that have overlapping substrate specificities. Expand
Effect of quinidine on the interconversion kinetics between haloperidol and reduced haloperidol in humans: implications for the involvement of cytochrome P450IID6
TLDR
HAL is a potent butyrophenone antipsychotic agent which is reversibly metabolized to reduced haloperidol (RHAL), and there is a significant increase in the AUC (0-t) and Cmax values following quinidine co-administration with either HAL or RHAL. Expand
Differential effects of quinidine on the disposition of nifedipine, sparteine, and mephenytoin in humans
TLDR
The interaction between quinidine and nifedipine supports the involvement of a common P450 (P450IIIA4) in the metabolism of the two drugs. Expand
Potent inhibition of yeast-expressed CYP2D6 by dihydroquinidine, quinidine, and its metabolites.
TLDR
Quinidine and the impurity dihydroquinidine are the important inhibitors of CYP2D6, as determined by the retention-time parameter k' using reverse-phase HPLC. Expand
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TLDR
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