Simple and reliable radioreceptor assay for beta-adrenoceptor antagonists and active metabolites in native human...

A radioreceptor assay (RRA) for the assay of beta-adrenoceptor antagonists in native human plasma is described. The hydrophilic antagonist 3H-CGP 12177 was used as the radioligand. In contrast to the hydrophobic radioligand 3H-dihydroalprenolol, which was investigated in parallel, the beta-adrenoceptor binding of 3H-CGP 12177 by rat reticulocyte membranes was found not to be affected by inclusion of increasing proportions (0-66% of incubation volume) of human plasma in the assay. Thus, solvent extraction of drug and/or active metabolites was not necessary to avoid binding of the radioligand tracer to plasma added in the RRA. The assay of unprocessed samples was possible. Drug concentrations in plasma after oral administration of propranolol (240 mg) or carteolol (30 mg) to 6 healthy volunteers were measured by the RRA and in parallel by a chemical method. The results from both methods agreed when the plasma concentration kinetics of propranolol were investigated (elimination half-life:3.9 h). In contrast, plasma concentrations of carteolol were consistently higher according to the RRA after oral administration of the drug. Identical concentrations, however, were found by the RRA and chemical method using plasma samples spiked with carteolol. Plasma concentrations of carteolol detected by the chemical method decline monoexponentially (elimination half-life: 5.4 h). A similar half-life of elimination for parent drug was found by the RRA (5.9 h), but an additional term describing the appearance of an active metabolite was necessary to account for the biphasic drug elimination (elimination half-life of metabolite: 17.3 h).(ABSTRACT TRUNCATED AT 250 WORDS)