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Interindividual differences in β‐receptor density contribute to variability in response to β‐adrenoceptor antagonists
Author(s) -
Zhou HongHao,
Silberstein David J,
Koshakji Richard P,
Wood Alastair J J
Publication year - 1989
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.1989.78
Subject(s) - propranolol , blockade , endocrinology , medicine , receptor , adrenergic receptor , chemistry , pharmacology
To determine the role of changes in receptor density and the considerable interindividual variability in the response to β‐adrenergic antagonists, we determined the relationship between the β‐blockade produced by propranolol and the β‐adrenergic receptor density (B max ) in 16 healthy subjects who received 10, 20, 40, and 80 mg propranolol every 8 hours for 1 day at each dosage level. The extent of β‐blockade produced was assessed as the reduction in exercise tachycardia. The extent of β‐blockade correlated with pretreatment lymphocyte B max (30 mg/day: r = 0.6290, p < 0.05; 60 mg/day: r = 0.5279, p < 0.05; 120 mg/day: r = 0.5888, p < 0.01; 240 mg/day: r = 0.6783, p < 0.005). When the extent of β‐blockade was corrected for plasma propranolol concentrations, the correlation was further improved (30 mg/day: r = 0.7636, p < 0.001; 60 mg/day: r = 0.7218, p < 0.002; 120 mg/day: r = 0.7814, p < 0.001; 240 mg/day: r = 0.6899,/> < 0.005). We conclude that the density of β‐adrenergic receptors is one of the principal factors that control β‐receptor response to antagonists in human beings. Clinical Pharmacology and Therapeutics (1989) 45 , 587–592; doi: 10.1038/clpt.1989.78