Multiple dosing increases the ocular bioavailability of topically administered flurbiprofen

Area of Science:

• Ophthalmology
• Pharmacokinetics
• Drug Delivery

Background:

• Topical ocular drug delivery is crucial for treating eye conditions.
• Understanding flurbiprofen's ocular bioavailability is key for effective anti-inflammatory treatment.
• Cyclo-oxygenase (COX) inhibition is a primary mechanism for NSAIDs like flurbiprofen.

Purpose of the Study:

• To determine the ocular bioavailability of radiolabeled flurbiprofen in rabbits.
• To compare ocular tissue concentrations after single versus multiple topical doses.
• To assess the impact of dose frequency and concentration on flurbiprofen's ocular distribution.

Main Methods:

• Radiolabeled flurbiprofen was administered topically to rabbits.
• Single and multiple dosing regimens (0.03% and 0.1% solutions) were employed.
• Ocular tissue concentrations were measured to assess bioavailability.

Main Results:

• Three doses of 0.03% flurbiprofen achieved concentrations inhibiting cyclo-oxygenase activity.
• Multiple dosing (three doses) yielded higher tissue concentrations than single doses.
• Increasing flurbiprofen concentration to 0.1% did not improve ocular bioavailability.
• Dose administration beyond three doses showed no significant increase in tissue concentration.

Conclusions:

• Multiple topical administrations of 0.03% flurbiprofen enhance ocular bioavailability in rabbits.
• Optimal therapeutic concentrations are achieved with three doses, with diminishing returns for additional doses or higher concentrations.
• These findings inform dosing strategies for topical flurbiprofen in ophthalmic applications.