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)-propranolol 80 mg, (S)-propranolol 80 mg, or rac-propranolol 160 mg was administered twice daily for 3 days. Multiple blood samples were collected for up to 12 hours on the fourth day to characterize the steady-state 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%) and as a pure enantiomer (15.8% versus 12.9%), respectively (p < 0.05). No stereoselective pharmacokinetic differences were observed between total (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.


CONCLUSIONS
Stereoselective steady-state pharmacokinetic differences in AUC(0-720) were observed between (R)- and (S)-propranolol.
Paradiso-Hardy
F L
FL
Department of Pharmacy, Sunnybrook Health Science Centre, and the Faculty of Pharmacy, University of Toronto, Ontario, Canada.
Walker
S E
SE
Bowles
S K
SK
D000328:Adult; D000959:Antihypertensive Agents / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001798:Blood Proteins / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D004311:Double-Blind Method; D006801:Humans; D008297:Male; D011433:Propranolol / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*; D012016:Reference Values; D013237:Stereoisomerism
D000959:Antihypertensive Agents; D001798:Blood Proteins; D011433:Propranolol