Summary
Following a cross-over design propranolol 20 mg p.o. was given to 7 healthy subjects at 09.00 h and 21.00 h at an interval of 1 week. Heart rate (HR) during submaximal ergometer exercise was measured at four intervals during 10 h after treatment. Plasma propranolol concentrations were also determined.
The suppressive effect (%R) of propranolol on the rise in HR during exercise after the morning dosage was significantly greater at 1.5 h and tended to be greater 3 h after administration than at comparable times in the evening trial. Mean plasma propranolol concentrations during the early phase were higher after the morning than the evening dose. The maximum plasma concentration (Cmax), area under the plasma concentration-time curve from 0 to 10 h (AUC (0–10)) and absorption rate constant (ka) were significantly greater after the morning dose. The time to maximum concentration (tmax) and elimination half-life (t1/2) of the morning and evening dosages did not differ. A significant correlation was observed between plasma propranolol concentration and %R in HR during exercise in the morning (r=0.74) and evening (r=0.63) trials, and the regression lines of the morning and evening treatments did not differ.
The data indicate that the suppressive effect of propranolol on exercise-induced tachycardia was relatively greater after a morning than an evening dose; that propranolol was more rapidly absorbed from the gastrointestinal tract after the morning than the evening dosage; that diurnal changes in the activity of propranolol depend in part on the time of administration and its subsequent effect on plasma concentrations of the drug; and that the antagonist activity of propranolol relative to a given drug concentration may not differ between morning and evening treatments.
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Fujimura, A., Kumagai, Y., Sugimoto, K. et al. Circadian influence on effect of propranolol on exercise-induced tachycardia in healthy subjects. Eur J Clin Pharmacol 38, 133–137 (1990). https://doi.org/10.1007/BF00265971
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DOI: https://doi.org/10.1007/BF00265971