Circadian influence on effect of propranolol on exercise-induced tachycardia in healthy subjects.
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 (t 1/2) 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Fujimura
A
A
Department of Clinical Pharmacology, Jichi Medical School, Tochigi, Japan.
Kumagai
Y
Y
Sugimoto
K
K
Nakashima
H
H
Kajiyama
H
H
Ebihara
A
A
Ohashi
K
K
D000293:Adolescent; D000328:Adult; D002940:Circadian Rhythm; D015444:Exercise; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D008297:Male; D011433:Propranolol / Q000097:blood / Q000494:pharmacology*
D011433:Propranolol