Summary
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.
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References
Aellig WH (1982) Clinical pharmacological experiments with bopindolol (LT 31-200): a long acting beta-adrenoceptor blocking drug with partial agonist activity. Br J Clin Pharmacol 13: 267–268 P
Barnett DB, Batta M, Davies B, Nahorski SR (1980) Evaluation of a radioreceptor assay for beta-adrenoceptor antagonists in plasma. Eur J Clin Pharmacol 17: 349–354
Dayer P, Courvoisier F, Balant L, Fabre J (1982a) Beta-blockers and drug oxidation status. Lancet 1: 509
Dayer P, Kubli A, Kupfer A, Courvoisier F, Balant L, Fabre J (1982b) Defective hydroxylation of bufuralol associated with side-effects of the drug in poor metabolisers. Br J Clin Phármacol 13: 750–752
Dayer P, Balant L, Kupfer A, Courvoisier F, Fabre J (1983a) Contribution of the genetic status of oxidative metabolism to variability in the plasma concentrations of beta-adrenoceptor blocking agents. Eur J Clin Pharmacol 24: 797–799
Dayer P, Leemann T, Gut J, Kronbach T, Kupfer A, Francis R, Meyer U (1985) Steric configuration and polymorphic oxidation of lipophilic beta-adrenoceptor blocking agents: in vivo — in vitro correlations. Biochem Pharmacol 34: 399–400
Engel G, Hoyer D, Berthold R, Wagner H (1981) (±)125Iodocyanopindolol, a new ligand for beta-adrenoceptors: identification and quantitation of subclasses of beta-adrenoceptors in guinea pig. Naunyn-Schmiedebergs Arch Pharmacol 317: 277–285
Evans DAP, Mahgoub A, Sloan TP, Idle JR, Smith RL (1980) A family and population study of the genetic polymorphism of debrisoquine oxidation in a white British population. J Med Genet 17: 102–105
Francis RJ, East PB, Larman J (1983) Kinetics and metabolism of (+), (−) and (±)-bufuralol. Eur J Clin Pharmacol 23: 529–533
Hermansson J, Von Bahr C (1982) Determination of (R)- and (S)-alprenolol and (R)- and (S)-metoprolol as their diastereomeric derivatives in human plasma by reversed-phase liquid chromatography. J Chromatogr 227: 113–127
Leemann T, Dayer P, Balant L, Buri P (1984) Direct determination of R- and S-metoprolol in biological fluids by ion-pair-HPLC. Abstract of the 16th Annual Meeting of the US GEB, March 1984, Zürich. Experientia 40: 647
Lennard MS, Silas JH, Freestone S, Trevethick J (1982) Defective metabolism of metoprolol in poor hydroxylators of debrisoquine. Br J Clin Pharmacol 14: 301–303
Lennard MS, Silas JH, Freestone S, Tucker GT, Ramsay LE, Woods HF (1983) Differential stereoselective metabolism of metoprolol in extensive and poor hydroxylators of debrisoquine. Br J Clin Pharmacol 15: 586–587 P
Scales B, Copsey PB (1975) The gas chromatographic determination of atenolol in biological samples. J Pharm Pharmacol 27: 430–433
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Dayer, P., Leemann, T., Marmy, A. et al. Interindividual variation of beta-adrenoceptor blocking drugs, plasma concentration and effect: Influence of genetic status on behaviour of atenolol, bopindolol and metoprolol. Eur J Clin Pharmacol 28, 149–153 (1985). https://doi.org/10.1007/BF00609683
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DOI: https://doi.org/10.1007/BF00609683