Polymorphic metabolism of beta-adrenoceptor antagonists.

  title={Polymorphic metabolism of beta-adrenoceptor antagonists.},
  author={J. H. Silas and Martin S. Lennard and Geoffrey T Tucker and Lawrence E. Ramsay and H. F. Woods},
  journal={British journal of clinical pharmacology},
  volume={17 Suppl 1},
  • J. Silas, M. Lennard, H. Woods
  • Published 1 February 1984
  • Biology, Chemistry, Medicine
  • British journal of clinical pharmacology
Most beta-adrenoceptor blockers undergo extensive oxidative metabolism. The evidence for polymorphism of the debrisoquine type is reviewed. The AUC and half-life of metoprolol were considerably greater in poor metabolisers (PM) of debrisoquine than in extensive metabolisers (EM). Metoprolol alpha-hydroxylation is impaired and O-dealkylation must also be affected. Polymorphism in the former route has been demonstrated in a population of 143 patients to be directly related to debrisoquine… 
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The oral clearance and beta-adrenoceptor antagonist activity of propranolol after single dose are not related to debrisoquine oxidation phenotype.
The relationship between debrisoquine oxidation phenotype and the pharmacokinetics and pharmacodynamics of propranolol were investigated and a large genetic influence on the metabolism and 8-adrenoceptor antagonist activity of metoprolol was demonstrated.
Defective Oxidation of Drugs: Pharmacokinetic and Therapeutic Implications
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