Interindividual differences in beta-receptor density contribute to variability in response to beta-adrenoceptor antagonists.
To determine the role of changes in receptor density and the considerable interindividual variability in the response to beta-adrenergic antagonists, we determined the relationship between the beta-blockade produced by propranolol and the beta-adrenergic receptor density (Bmax) 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 beta-blockade produced was assessed as the reduction in exercise tachycardia. The extent of beta-blockade correlated with pretreatment lymphocyte Bmax (30 mg/day: r = 0.6290, p less than 0.05; 60 mg/day: r = 0.5279, p less than 0.05; 120 mg/day: r = 0.5888, p less than 0.01; 240 mg/day: r = 0.6783, p less than 0.005). When the extent of beta-blockade was corrected for plasma propranolol concentrations, the correlation was further improved (30 mg/day: r = 0.7636, p less than 0.001; 60 mg/day: r = 0.7218, p less than 0.002; 120 mg/day: r = 0.7814, p less than 0.001; 240 mg/day: r = 0.6899, p less than 0.005). We conclude that the density of beta-adrenergic receptors is one of the principal factors that control beta-receptor response to antagonists in human beings.
Zhou
H H
HH
Division of Clinical Pharmacology, Vanderbilt University School of Medicine, Nashville, TN 37232.
Silberstein
D J
DJ
Koshakji
R P
RP
Wood
A J
AJ
D000328:Adult; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism; D008297:Male; D005082:Physical Exertion; D011433:Propranolol / Q000097:blood / Q000494:pharmacology*; D011943:Receptors, Adrenergic, beta / Q000032:analysis* / Q000187:drug effects
D011943:Receptors, Adrenergic, beta; D011433:Propranolol