Initial evaluation of transdermal timolol: serum concentrations and beta-blockade

Area of Science:

• Pharmacology
• Dermatology

Background:

• Timolol is a beta-blocker commonly used in ophthalmic solutions.
• Transdermal drug delivery offers potential for sustained systemic absorption.
• Evaluating dermal application of timolol requires assessment of serum concentrations and physiological effects.

Purpose of the Study:

• To evaluate serum concentrations and beta-blockade following transdermal application of timolol ointment.
• To determine the relationship between serum timolol levels and heart rate response during exercise.
• To assess the safety and delivery efficiency of transdermal timolol.

Main Methods:

• Six healthy males received placebo or timolol base (30 or 60 mg) via dermal patches for 30 hours.
• Serum timolol concentrations were measured using a radioligand receptor assay.
• Heart rate was monitored during bicycle ergometry before and at various time points post-application.

Main Results:

• Measurable therapeutic serum concentrations of timolol were achieved in all subjects.
• Significant beta-blockade was observed, with reduced exercise-induced heart rates (p < 0.05).
• A strong correlation (r = -0.92) was found between log timolol serum concentration and heart rate reduction.

Conclusions:

• Transdermal timolol ointment effectively delivers the drug systemically, achieving therapeutic levels and beta-blockade.
• The observed dose-dependent reduction in heart rate suggests potential for treating conditions responsive to beta-blockers.
• Minimal skin irritation and efficient drug delivery (50-60%) support further investigation into clinical applications.