Relationships among timolol doses, plasma concentrations and beta-adrenoceptor blocking activity

Area of Science:

• Pharmacology
• Cardiovascular Physiology

Background:

• Beta-adrenoceptor antagonists like timolol are used to manage cardiovascular conditions.
• Understanding the dose-response relationship and pharmacokinetics is crucial for effective therapeutic use.

Purpose of the Study:

• To investigate the relationship between timolol dosage, plasma concentration, and beta-adrenoceptor blockade.
• To assess the effects of single and repeated doses on exercise-induced tachycardia.

Main Methods:

• Six healthy male subjects received single and repeated doses of timolol (0.5-20 mg) or placebo.
• Exercise-induced tachycardia was measured using bicycle ergometry.
• Plasma timolol concentrations were analyzed.

Main Results:

• Maximal suppression of exercise-induced tachycardia was dose-dependent and occurred 2 hours post-dose.
• A plasma timolol concentration of 27 ng/ml correlated with maximal tachycardia suppression.
• Significant beta-adrenoceptor blockade was observed up to 12 hours on the last dosing day.

Conclusions:

• Timolol exhibits a clear dose-response relationship for suppressing exercise-induced tachycardia.
• Achieving maximal blockade requires specific plasma concentrations of timolol.
• Repeated dosing did not significantly alter the suppression of exercise-induced tachycardia or plasma concentration-time profiles.