STEADY-STATE PHARMACOKINETICS OF PROPRANOLOL ENANTIOMERS IN HEALTHY MALE-VOLUNTEERS

Objective: To describe the steady-state pharmacokinetics of (R)-, (S)- and racemic (rac) propranolol in 15 normotensive, male volunteers in a double-blind, randomized, 3-way, crossover study. Methods: (R)-propr anolol 80 mg, (S)-propranolol 80 mg, or rac-propranolol 160 mg was adm inistered twice daily for 3 days. Multiple blood samples were collecte d for up to 12 hours on the fourth day to characterize the steady-stat e pharmacokinetic profile of each enantiomer. Results: (R)-propranolol bound to plasma proteins to a lesser extent than (S)-propranolol when it was administered both as a racemic mixture (15.8% versus 13.0%) an d as a pure enantiomer (15.8% versus 12.9%), respectively (p < 0.05). No stereoselective pharmacokinetic differences were observed between t otal (bound and unbound) and unbound (R)- and (S)-propranolol. The AUC (0-720) of (R)-propranolol was significantly higher when administered as a racemic mixture than when given as a pure enantiomer (p < 0.01), suggesting the disposition of (R)-propranolol may be influenced by (S) -propranolol. Conclusion: Stereoselective steady-state pharmacokinetic differences in AUC(0-720) were observed between (R)- and (S)-proprano lol.