Concentration kinetics of propranolol, bisoprolol, and atenolol in humans assessed with chemical detection and a subtype-selective beta-adrenoceptor assay.

After oral administration of single doses of 240 mg of (+/-)propranolol (prop), 200 mg of (+/-)-atenolol (aten), and 100 mg of (+/-)-bisoprolol (biso) to six healthy male volunteers, the plasma concentration time profile was investigated. To measure total plasma concentrations of the parent racemic mixture of drug administered, a HPLC-assay of drug concentrations was used. To detect active metabolites and stereoselective pharmacokinetics of the racemates, plasma concentrations were also monitored by means of a subtype-selective receptor assay, using a beta 1-adrenoceptor preparation from rat salivary glands. It is shown that relevant amounts of active metabolites do not become apparent for either of the three drugs investigated. Furthermore, for neither of them can significant stereoselective elimination characteristics be seen. Monophasic elimination characteristics with t1/2 of 4.8 +/- 0.42 (prop), 6.87 +/- 0.46 (aten), and 9.19 +/- 0.38 h (biso) become apparent. The maximum concentrations observed after administration of the doses mentioned previously were 220 +/- 71 (prop), 904 +/- 104 (aten), and 445 +/- 32 (biso) (ng/ml plasma). One can conclude from comparison with the results from receptor-binding studies that the 100 mg dose of biso is five- to seven-fold more potent than the 200 mg dose of aten, with respect to antagonism versus beta 1-adrenoceptor-mediated effects.