Interindividual pharmacokinetic and pharmacodynamic variability of different beta blockers.

Hepatic drug metabolism influenced by genetic and environmental factors is a major source of variation in the response to a number of beta-adrenoceptor antagonists. The first study described here was carried out to define the role of a genetic determinant (debrisoquine-type oxidation polymorphism) on plasma concentration of bopindolol and its pharmacological effect. Atenolol was used as a negative and metoprolol as a positive control.

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.

Influence of renal failure on the hepatic clearance of bufuralol in man.

The beta-blocking agent bufuralol is subject to first-pass metabolism and is eliminated from the body almost entirely by biotransformation. Its major metabolite in plasma (1'-hydroxy-bufuralol) is biologically active and may contribute to the pharmacological effect of the drug. The effect of renal failure on the behavior of the parent compound and three of its metabolites was studied by comparing their kinetics in normal volunteers and in patients with severe renal insufficiency.

[Clearance concept applied to pharmacokinetics: 2. Experience with tolamolol (beta-blocking agent) in renal insufficiency (author's transl)].

Tolamolol is subject to first-pass metabolism and is eliminated from the body almost entirely by biotransformation. Its major metabolite in plasma (4-hydroxy-tolamolol) is biologically active and may contribute to the pharmacological effect of the drug. The effect of renal failure on the behaviour of the parent compound and of its metabolite was studied by comparing their kinetics in normal volunteers and in patients with severe renal insufficiency.