title: Extent of beta 1- and beta 2-receptor occupancy in plasma assesses the antagonist activity of metoprolol, pindolol, and propranolol in the elderly.
abstract: We estimated antagonist activity of metoprolol, pindolol, and propranolol in elderly cardiovascular patients by determining the extent to which the drugs occupied rabbit lung beta 1- and rat reticulocyte beta 2-adrenoceptors in plasma samples during drug treatment. The randomized, double-blind, crossover study was carried out by administering twice daily 100 mg metoprolol, 5 mg pindolol, and 80 mg propranolol for 7 days to 20 hypertensive subjects with a mean age of about 70 years. A 2-week interval was kept between administration of the different regimens. Receptor occupancy was measured at 1 hour before and 2 hours after administration of the last dose of each regimen by adding rabbit lung beta 1- and rat reticulocyte beta 2-receptors to plasma samples and by labeling the receptors with a radiolabeled beta-antagonist, (-)-[3H]CGP-12177. The results and conclusions were the following: (a) The extent to which metoprolol, pindolol, and propranolol occupied rabbit lung beta 1- and rat reticulocyte beta 2-adrenoceptors in plasma samples estimated accurately the intensity of beta-receptor antagonism in the patients who did not tolerate physiological and pharmacological tests measuring the degree of beta 1- and beta 2-adrenoceptor blockade. (b) The mean beta 1- and beta 2-receptor occupancy of pindolol and propranolol varied between 76% and 99% during the treatments. The mean beta 1-receptor occupancy of the metoprolol regimen varied between 54% and 92%, and its beta 2-receptor occupancy varied between 6% and 38%. Thus the antagonist activity of the metoprolol regimen differed significantly from that of the other regimens (ANOVA for repeated measures, p < 0.05 and 0.001, for the beta 1- and beta 2-occupancy, respectively). (c) The extent of beta 1- and beta 2-receptor occupancy in plasma samples was in conformity with the literature on the intensity, selectivity, and duration of beta-blockade after similar drug doses. (d) The data on the receptor occupancy of beta-blocking drugs in plasma samples appear to be valuable in analyzing their effects, and it may be a method for optimizing drug therapy for aged cardiovascular patients.
authors.affiliation: Department of Clinical Pharmacology, University of Turku, Finland.
authors.forename: T
authors.initials: T
authors.lastname: Kaila
authors.forename: E
authors.initials: E
authors.lastname: Iisalo
authors.forename: A
authors.initials: A
authors.lastname: Lehtonen
authors.forename: H
authors.initials: H
authors.lastname: Saarimaa
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000097:blood / Q000494:pharmacology*; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000188:drug therapy; D007700:Kinetics; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D008297:Male; D008790:Metoprolol / Q000097:blood / Q000494:pharmacology; D008875:Middle Aged; D010869:Pindolol / Q000097:blood / Q000494:pharmacology; D011433:Propranolol / Q000097:blood / Q000494:pharmacology; D011817:Rabbits; D018342:Receptors, Adrenergic, beta-1 / Q000378:metabolism; D018343:Receptors, Adrenergic, beta-2 / Q000378:metabolism*; D012156:Reticulocytes / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure
chemical_list: D000319:Adrenergic beta-Antagonists; D018342:Receptors, Adrenergic, beta-1; D018343:Receptors, Adrenergic, beta-2; D011433:Propranolol; D010869:Pindolol; D008790:Metoprolol