The effect of propranolol on exercise induced tachycardia is determined by plasma concentration and the density of adrenergic receptors on leukocytes.
The chronotropic response to a single oral dose of propranolol in 23 healthy subjects has been related to the plasma propranolol concentration and the density of beta-adrenoceptors on peripheral polymorphonuclear leucocytes. The percentage reduction in exercise-induced tachycardia was significantly correlated with the log plasma propranolol concentration within subjects but not between subjects. Taking the concentration of the active metabolite 4-hydroxypropranolol into account did not improve the interindividual correlation. The reduction in exercise-induced tachycardia was significantly correlated with the maximum binding density of (125I)-hydroxybenzylpindolol on polymorphonuclear leucocyte membrane fragments measured before medication. A response index (% reduction in exercise-induced tachycardia/plasma propranolol concentration) was correlated with the maximum binding density of (125I)-hydroxybenzylpindolol (pre-drug) at 2 h (rs = 0.72), 4 h (rs = 0.84) and 6 h (rs = 0.73) after dosing. The data suggest that interindividual variation in the response to propranolol after a single oral dose is determined by interindividual differences both in plasma propranolol and adrenoceptor density.
D000328:Adult; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D007962:Leukocytes / Q000187:drug effects*; D008297:Male; D009504:Neutrophils / Q000187:drug effects; D005082:Physical Exertion; D010869:Pindolol / Q000031:analogs & derivatives; D011433:Propranolol / Q000031:analogs & derivatives / Q000097:blood / Q000494:pharmacology*; D011941:Receptors, Adrenergic / Q000187:drug effects*
D011941:Receptors, Adrenergic; C001422:4-hydroxypropranolol; C012357:hydroxybenzylpindolol; D011433:Propranolol; D010869:Pindolol