Pharmacodynamics of racemic and S(-)-atenolol in humans.
The cardiovascular actions of racemic atenolol (RSATN) have been well characterized in humans, but the actions of S(-)-atenolol (SATN) when administered alone are unknown. In this study, responses of heart rate (HR) and Doppler-derived aortic blood flow profiles to upright treadmill exercise were compared after oral administration of 50 mg SATN and 100 mg RSATN in eight healthy, adult, male volunteers. After a single-blind, placebo run-in period, subjects were randomly allocated in a double-blind, crossover fashion to receive SATN and RSATN. Each study period was separated by a 7-day washout period. Multiple submaximal exercise tests were performed and data were collected over the 24 hours after each treatment. Both SATN and RSATN significantly (P < .05) blunted peak exercise HR by 38 +/- 3 and 37 +/- 3 beats/min, respectively. Aortic blood flow acceleration measured during peak exercise decreased after SATN and RSATN, by 13 +/- 4 and 13 +/- 3 m/sec2, respectively (P < .05). No difference in hemodynamic effect was observed between treatments. Pharmacodynamic parameters derived from plasma S(-)-atenolol concentration-effect (HR) curves after SATN, RSATN, and total atenolol plasma concentrations after RSATN did not differ significantly. Predicted maximum reductions in heart rate (Emax) and EC50 for S(-)-atenolol after SATN were 39.6 +/- 5.8 beats/min and 38.4 +/- 40.9 ng/ml versus 34.5 +/- 8 beats/min and 25.9 +/- 29.9 ng/ml for RSATN, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
University of Kentucky, College of Pharmacy, Lexington 40536-0084.
R A
RA
McCoy
G D
GD
Clifton
W A
WA
Clementi
M D
MD
Smith
T Q
TQ
Garvey
D P
DP
Wermeling
S E
SE
Schwartz
D000328:Adult; D001262:Atenolol / Q000008:administration & dosage / Q000494:pharmacology*; D001783:Blood Flow Velocity / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005080:Exercise Test / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D007536:Isomerism; D008297:Male; D016037:Single-Blind Method
D001262:Atenolol