In a randomized, double‐blind, crossover study in 10 healthy volunteers the hemodynamic effects, drug plasma concentrations, and thyroid hormone profiles were compared after oral administration for 1 week of 40 mg t.i.d. racemic (R,S)‐propranolol versus 20 mg t.i.d. optically pure (S)‐propranolol. During exercise, both substances decreased heart rate (−14%, p < 0.01), as well as the overall rate pressure product (−19%, p < 0.01) to the same extent, indicating similar β‐blocking effects. After oral application of (R,S)‐propranolol the maximal plasma concentration (C_max) and the area under the plasma concentration—time curve (AUC) of (S)‐propranolol were higher than those of (R)‐propranolol (eudismic ratios (S)‐ over (R)‐propranolol C_max, 1.36 p < 0.01] and AUC, 1.42 p < 0.01]) despite dose‐equivalence of both enantiomers in the administered racemic (R,S)‐propranolol preparation indicating different pharmacokinetic properties. Mean values of C_max and the AUC of (S)‐propranolol did not differ significantly after 1 week of oral administration of 40 mg (R,S)‐propranolol and 20 mg (S)‐propranolol t.i.d., respectively. The ratio of triiodothyronine to thyroxine was decreased by (R,S)‐propranolol (− 25%, p < 0.01) but not by (S)‐propranolol, suggesting that only the (R)‐enantiomer inhibits the conversion of thyroxine to triiodothyronine. Thus, half‐dosed optically pure (S)‐propranolol is an equally effective β‐adrenergic receptor antagonist compared with currently used racemic (R,S)‐propranolol. By contrast, the conversion of thyroxine to triiodothyronine is inhibited by (R)‐propranolol only. Because there is an efficient method available to separate the (R)‐ and (S)‐enantiomers of propranolol they should be used as optically pure drugs according to their specific indications rather than racemic (R,S)‐propranolol.

Clinical Pharmacology and Therapeutics (1992) 51, 445–453; doi:10.1038/clpt.1992.45