EXERCISE INCREASES PLASMA-CONCENTRATIONS OF (R)-PROPRANOLOL AND (S)-PROPRANOLOL

Objective: We recently reported a highly stereoselective increase in p lasma concentrations of (S)-atenolol during exercise which is most lik ely due to a release of the drug from adrenergic cells. The objective of the present study was to investigate the influence of physical exer cise on plasma concentrations of the (R)-and (S)-enantiomers of propra nolol. Methods: Blood samples were taken immediately before and at the end of exercise in 12 patients receiving chronic treatment with racem ic (R, S)-propranolol. Plasma concentrations of (R)- and (S)-propranol ol were determined by HPLC. Results. In contrast to atenolol, mean pla sma concentrations of (S)-propranolol were significantly higher (+20%) than those of (R)-propranolol at rest. During exercise there was an i ncrease in plasma concentrations of both (R)-propranolol (+129%) and ( S)-propranolol (+109%). Conclusion: 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 a drenergic nerves, whereas the reason for the increase in (R)-propranol ol remains to be determined. This release of the beta-adrenoceptor blo cking (S)-enantiomer directly at the synaptic gaps might be one reason for the poor correlation between plasma concentration and effect of b eta-adrenoceptor antagonists repeatedly described in the literature.