Haemodynamics of carvedilol in normal subjects compared with propranolol, pindolol, and labetalol.
Single doses, in log steps, of carvedilol from 12.5 to 200 mg, propranolol 40 to 320 mg, pindolol 2.5 to 20 mg, labetalol 50 to 400 mg, and placebo control were given randomised double blind to six healthy volunteers. Noninvasive measurements of blood pressure and heart rate were made supine, standing, and during cycle exercise 1 and 2 h postdose. All drugs produced a dose-dependent reduction in exercise heart rate, but this was greater for propranolol and pindolol than for carvedilol and labetalol at the dose studied. Exercise systolic blood pressure was similarly reduced but there was less separation in the dose response curves between the various drugs. Supine and standing heart rate was reduced only by propranolol, but supine systolic blood pressure was reduced by carvedilol (50, 100, and 200 mg), propranolol (40, 160, and 320 mg), pindolol (5, 10, and 20 mg), and labetalol (400 mg). Standing systolic blood pressure was reduced by carvedilol (50, 100, and 200 mg) and pindolol (2.5 and 20 mg). The effects of carvedilol on resting blood pressure suggest additional blood pressure lowering properties other than the pure beta-antagonism of propranolol. Effects on exercise heart rate and systolic blood pressure were similar to carvedilol (12.5-200 mg) with labetalol (50-400 mg), but changes in resting systolic blood pressure were less consistent with labetalol.
Tomlinson
B
B
Department of Clinical Pharmacology, University College and Middlesex School of Medicine, London, England.
Cronin
C J
CJ
Graham
B R
BR
Prichard
B N
BN
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D002227:Carbazoles / Q000494:pharmacology*; D000077261:Carvedilol; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D007741:Labetalol / Q000494:pharmacology; D008297:Male; D005082:Physical Exertion; D010869:Pindolol / Q000494:pharmacology; D011412:Propanolamines / Q000494:pharmacology*; D011433:Propranolol / Q000494:pharmacology; D011897:Random Allocation
D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D002227:Carbazoles; D011412:Propanolamines; D000077261:Carvedilol; D011433:Propranolol; D010869:Pindolol; D007741:Labetalol