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Effect of Celiprolol, a New Beta 1 ‐Alpha 2 Blocker, on the Cardiovascular Response to Exercise
Author(s) -
Caruso Frank S.,
Berger Bruce M.,
Darragh Austin,
Weng Teng,
Vukovich Robert
Publication year - 1986
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1002/j.1552-4604.1986.tb02899.x
Subject(s) - celiprolol , atenolol , heart rate , propranolol , placebo , medicine , blood pressure , pindolol , beta blocker , anesthesia , cardiology , heart failure , alternative medicine , pathology
The pharmacodynamics of beta blockade with single oral doses of celiprolol 200 and 400 mg, compared with placebo, atenolol 50 and 100 mg, propranolol 80 and 160 mg, metoprolol 100 and 200 mg, and pindolol 5 and 10 mg, were evaluated in an open, incomplete‐block study design employing 11 healthy male volunteers. Each subject received five of the 11 possible treatments at weekly intervals. The maximal rate‐pressure product (RPP) induced by standardized treadmill exercise was measured 1, 2, 4, 6, 8, 12, 24, 36, and 48 hours after each treatment. During the course of the exercise test, heart rate and systolic blood pressure were recorded at one‐minute intervals for five minutes. The maximal RPP, heart rate, and the maximum change from baseline were calculated for each exercise period. The data were analyzed using absolute reduction and percentage reduction of these parameters. All of the beta blockers tested produced significant decreases ( P < .05) in the exercise RPP, ranging from 16% reduction for celiprolol 200 mg to 47% reduction for propranolol 160 mg at peak response. Celiprolol 400 mg reduced the RPP by 31% at peak effect and did not differ significantly from the other treatments. Celiprolol 400 mg and atenolol 100 mg were the only agents that significantly reduced the RPP 24 hours posttreatment (20.7% and 21.7%, respectively) compared with placebo. Celiprolol 400 mg was the only agent to significantly reduce exercise heart rate 24 hours posttreatment (26.6 beats , P < .05). Pharmacodynamic half‐lives, calculated by means of linear regression analysis using absolute reduction of RPP, ranged from 13.2 hours for propranolol 80 mg to 24.1 hours for celiprolol 400 mg. Thus, celiprolol appears to have pharmacologic duration of effect in excess of its plasma elimination half‐life, and should be suitable for once‐daily administration in patients .