Cardiovascular beta-adrenergic blocking effects of bornaprolol in humans: relation to dose and plasma concentration.
The cardiovascular beta-blocking effects of bornaprolol were studied in healthy male volunteers after four single oral doses. The inhibition of isoproterenol-induced tachycardia was monitored for 72 h in six subjects, and the inhibition of exercise-induced tachycardia and rise of systolic blood pressure were monitored for 167 h in six other subjects. Plasma drug concentrations were determined by gas chromatography. Bornaprolol significantly reduced the resting heart rate, isoproterenol- and exercise-induced tachycardia, and effort hypertension. The peak effect was obtained within 1-2 h of drug administration and was correlated with dose. The effect on the isoproterenol test remained significant for 6 h after administration of 40 mg bornaprolol, and 72 h after 80, 120, and 240 mg. The effect of bornaprolol on the exercise test in comparison with placebo was significant during 23 h (120 and 240 mg) and 47 h (480 and 960 mg). A positive relationship was found for both tests between the maximum effect and the doses administered. A correlation was also found for each group of subjects between the time course of the plasma drug concentration and the effects of each bornaprolol dose on isoproterenol- and exercise-induced tachycardia. The beta-blocking effects in individual subjects, however, often continued long after the disappearance of detectable plasma drug concentrations.
D000284:Administration, Oral; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D003331:Coronary Vessels / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D005082:Physical Exertion; D011412:Propanolamines / Q000008:administration & dosage / Q000097:blood* / Q000494:pharmacology
D000319:Adrenergic beta-Antagonists; D011412:Propanolamines; C018417:bornaprolol; D007545:Isoproterenol