Exercise increases plasma concentrations of (R)- and (S)-propranolol.
OBJECTIVE
We recently reported a highly stereoselective increase in plasma concentrations of (S)-atenolol during exercise which is most likely due to a release of the drug from adrenergic cells. The objective of the present study was to investigate the influence of physical exercise on plasma concentrations of the (R)- and (S)-enantiomers of propranolol.


METHODS
Blood samples were taken immediately before and at the end of exercise in 12 patients receiving chronic treatment with racemic (R, S)-propranolol. Plasma concentrations of (R)- and (S)-propranolol were determined by HPLC.


RESULTS
In contrast to atenolol, mean plasma concentrations of (S)-propranolol were significantly higher (+20%) than those of (R)-propranolol at rest. During exercise there was an increase in plasma concentrations of both (R)-propranolol (+129%) and (S)-propranolol (+109%).


CONCLUSIONS
Based on information from in vitro studies we conclude that the increase in plasma concentrations of (S)-propranolol during exercise is caused by a release of the drug from adrenergic nerves, whereas the reason for the increase in (R)-propranolol remains to be determined. This release of the beta-adrenoceptor blocking (S)-enantiomer directly at the synaptic gaps might be one reason for the poor correlation between plasma concentration and effect of beta-adrenoceptor antagonists repeatedly described in the literature.
Stoschitzky
K
K
Institute of Pharmaceutical Chemistry, Karl Franzens University, Graz, Austria.
Schumacher
M
M
Stark
G
G
Dimai
H P
HP
Stauber
R
R
Stoschitzky
P
P
Krejs
G J
GJ
Klein
W
W
Lindner
W
W
D000319:Adrenergic beta-Antagonists / Q000097:blood*; D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D001794:Blood Pressure / Q000187:drug effects; D015444:Exercise / Q000502:physiology*; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D008968:Molecular Conformation; D011433:Propranolol / Q000097:blood*; D013237:Stereoisomerism
D000319:Adrenergic beta-Antagonists; D011433:Propranolol