Single dose pharmacokinetics of (S)-atenolol administered orally as a single enantiomer formulation and as a racemic mixture (Tenormin).
The purpose of this study was to describe the pharmacokinetics of and heart rate and blood pressure responses to (S)-atenolol (SATN) and (R)-atenolol (RATN) after oral administration of (S)-atenolol and (R,S)-atenolol (Tenormin) in man. Eight male subjects were given single oral doses of 50 mg of SATN as a single enantiomer formulation (SEF) and 100 mg of Tenormin (TMN) using a randomized, double-blind, 2-period, complete crossover study design. Subjects performed exercise tolerance tests (Bruce Protocol) before and 2, 4, 6, 8, 12, and 24 h after drug administration. Plasma samples were obtained 2 min before and 30 min, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, and 24 h after dosing. Urine was collected for the first 48 h after dosing. Plasma and urine samples were analyzed for SATN and RATN by an enantioselective HPLC method. SEF and Tenormin attenuate exercise-induced increases in heart rate and systolic blood pressure. Mean changes in exercise heart rates 4 h after dosing were -38 +/- 3 bpm and -37 +/- 3 bpm for SEF and TMN, respectively, P = 0.792. Mean changes in exercise systolic blood pressure were -42 +/- 12 mm Hg and -55 +/- 14 mm Hg for SEF and TMN, respectively, P = 0.484. Mean area under the plasma level time curve (AUC0-24) and mean Cmax for SATN for SEF were significantly lower than for SATN after TMN.(ABSTRACT TRUNCATED AT 250 WORDS)
Clementi & Associates Ltd., Radnor, Pennsylvania.
W A
WA
Clementi
T Q
TQ
Garvey
G D
GD
Clifton
R A
RA
McCoy
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S
Brandt
S
S
Schwartz
D000284:Administration, Oral; D001262:Atenolol / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology*; D001682:Biological Availability; D004311:Double-Blind Method; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D005082:Physical Exertion; D011897:Random Allocation; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013599:Systole / Q000187:drug effects*
D001262:Atenolol