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Related Experiment Videos

Dosing rate-dependent relationship between propranolol plasma concentration and beta-blockade

H Takahashi1, H Ogata, K Kashiwada

  • 1Department of Biopharmaceutics, Meiji College of Pharmacy, Tokyo, Japan.

The Journal of Pharmacology and Experimental Therapeutics
|May 1, 1993
PubMed
Summary

The dosing rate of propranolol significantly impacts its beta-blockade effect, with sustained release formulations showing a greater heart rate reduction. This suggests formulation influences drug efficacy and concentration-response relationships.

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Area of Science:

  • Pharmacology
  • Cardiovascular Medicine

Background:

  • Beta-blockers like propranolol are crucial in managing cardiovascular conditions.
  • Understanding the pharmacokinetics and pharmacodynamics of drug delivery is essential for optimizing therapeutic outcomes.

Purpose of the Study:

  • To investigate the influence of propranolol dosing rate on beta-blockade.
  • To compare the effects of conventional tablets versus sustained-release capsules on propranolol's concentration-response relationship.

Main Methods:

  • Human volunteers received conventional propranolol tablets and sustained-release capsules.
  • Plasma propranolol concentrations and heart rate reductions were measured.
  • Animal models (rabbits) and isolated guinea pig atrial preparations were used to study concentration-response curves and hysteresis.

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Main Results:

  • Sustained-release propranolol demonstrated a steeper heart rate reduction slope compared to conventional tablets.
  • A leftward shift in the plasma concentration-response curve was observed with decreased propranolol infusion rates in rabbits.
  • Anticlockwise hysteresis in the temporal response was noted for propranolol but not for hydrophilic beta-blockers like atenolol.

Conclusions:

  • Propranolol dosing rate and formulation significantly affect its beta-blockade efficacy and concentration-response dynamics.
  • The observed effects are independent of sympathetic activation.
  • Hydrophilic beta-blockers exhibit different concentration-response relationships compared to propranolol.