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  • Title: Steady-state pharmacokinetics of propranolol enantiomers in healthy male volunteers.
    Author: Paradiso-Hardy FL, Walker SE, Bowles SK.
    Journal: Int J Clin Pharmacol Ther; 1998 Jul; 36(7):370-5. PubMed ID: 9707351.
    Abstract:
    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. CONCLUSION: Stereoselective steady-state pharmacokinetic differences in AUC(0-720) were observed between (R)- and (S)-propranolol.
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