Ocular timolol levels after drug withdrawal: an experimental model

Area of Science:

• Ophthalmology
• Pharmacology
• Ocular Toxicology

Background:

• Topical timolol maleate is a common treatment for glaucoma.
• Understanding the ocular tissue distribution and retention of timolol is crucial for optimizing its therapeutic efficacy and minimizing side effects.

Purpose of the Study:

• To investigate the ocular tissue distribution and long-term retention of carbon 14-labelled timolol maleate in pigmented rabbits following repeated topical administration.

Main Methods:

• Carbon 14-labelled timolol maleate was administered daily to the eyes of 12 pigmented rabbits for 42 days.
• Ocular tissues and aqueous humor drug levels were quantified up to 42 days after cessation of treatment.

Main Results:

• Timolol maleate demonstrated significant concentration in melanotic ocular tissues.
• Slow drug release was observed, with detectable levels in pigmented tissues persisting for 42 days post-withdrawal.
• Timolol was present in the aqueous humor for up to 5 days after drug withdrawal.

Conclusions:

• The prolonged presence of timolol in ocular tissues, particularly melanotic ones, contributes to its long-term ocular hypotensive effect.
• Findings suggest that the dosage or frequency of topical timolol maleate may need adjustment in glaucoma patients, especially those with significant pigmentation.