Interindividual variation of beta-adrenoceptor blocking drugs, plasma concentration and effect: influence of genetic status on behaviour of atenolol, bopindolol and metoprolol.
Ten healthy subjects whose genetic oxidative phenotype had been determined (6 extensive and 4 poor metabolizers of the debrisoquine-sparteine type of polymorphism) received single oral doses of 3 beta-blockers: atenolol, bopindolol and metoprolol. The plasma concentrations and the extent of the decrease in exercise-induced tachycardia were determined. The oxidative polymorphism was only significant for substances that had a high hepatic first pass metabolism, such as metoprolol. The metabolic pathway under genetic control was highly stereoselective. This observation must be taken into account when assessing the relation between the plasma concentration and effect of these drugs, which are often administered as racemic mixtures.
Dayer
P
P
Leemann
T
T
Marmy
A
A
Rosenthaler
J
J
D000319:Adrenergic beta-Antagonists / Q000097:blood* / Q000494:pharmacology; D000328:Adult; D001262:Atenolol / Q000097:blood* / Q000494:pharmacology; D006801:Humans; D007206:Individuality; D008790:Metoprolol / Q000097:blood* / Q000494:pharmacology; D010084:Oxidation-Reduction; D010869:Pindolol / Q000031:analogs & derivatives* / Q000097:blood / Q000494:pharmacology; D011110:Polymorphism, Genetic
D000319:Adrenergic beta-Antagonists; D001262:Atenolol; D010869:Pindolol; D008790:Metoprolol; C036007:bopindolol