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Related Experiment Videos

Timolol and propranolol: bioavailability, plasma concentrations, and beta blockade

T W Wilson, W B Firor, G E Johnson

    Clinical Pharmacology and Therapeutics
    |December 1, 1982
    PubMed
    Summary

    Timolol exhibits higher bioavailability and lower systemic clearance than propranolol, leading to predictable pharmacologic responses from oral doses. These physicochemical differences impact drug absorption and therapeutic effects.

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    Area of Science:

    • Pharmacology
    • Clinical Pharmacy
    • Drug Metabolism

    Background:

    • Timolol and propranolol are nonselective beta-adrenergic blockers.
    • Timolol is less lipid-soluble and a single enantiomer, unlike racemic propranolol.
    • Differences in physicochemical properties may affect bioavailability, clearance, and pharmacologic response.

    Purpose of the Study:

    • To compare the bioavailability, systemic clearance, and pharmacologic response of timolol and propranolol.
    • To investigate the impact of physicochemical differences on drug behavior and efficacy.
    • To determine if oral dose responses correlate with intravenous responses for both drugs.

    Main Methods:

    • Double-blind, randomized crossover study in 10 healthy subjects.
    • Administration of placebo, intravenous (IV) and oral propranolol, and IV and oral timolol.

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  • Monitoring of plasma drug concentrations and heart rate response to exercise.

    • Main Results:

    • Timolol demonstrated greater bioavailability (0.61 vs. 0.32) and lower systemic clearance (463 vs. 1040 ml kg-1 hr-1) compared to propranolol.
    • Pharmacologic response to oral timolol correlated with IV response and plasma concentration, unlike propranolol.
    • Half-lives were similar for both drugs (2.7 hr for timolol, 2.9 hr for propranolol).

    Conclusions:

    • Timolol's physicochemical properties result in enhanced bioavailability.
    • Pharmacologic response to oral timolol is predictable from IV administration and reflects plasma levels.
    • Unlike propranolol, timolol's therapeutic effects are more directly linked to its concentration and predictable dosing.