Ocular and systemic bioavailability of ophthalmic flurbiprofen

Area of Science:

• Pharmacokinetics and Drug Metabolism
• Ocular Pharmacology
• Nonsteroidal Anti-inflammatory Drugs (NSAIDs)

Background:

• Flurbiprofen is a nonsteroidal anti-inflammatory drug (NSAID) that is not metabolized in the eye.
• Understanding the relationship between systemic and ocular drug circulation is crucial for effective ophthalmic drug delivery.
• NSAIDs are widely used for managing ocular inflammation and pain.

Purpose of the Study:

• To investigate the drug kinetic relationship between systemic and ocular humoral circulation using flurbiprofen as a probe compound.
• To quantify the ocular and systemic bioavailabilities of topically administered flurbiprofen.
• To elucidate the elimination pathways of flurbiprofen from the ocular compartment.

Main Methods:

• Anesthetized albino rabbits received intravenous, topical, and intracameral doses of flurbiprofen.
• Aqueous humor and plasma samples were collected for pharmacokinetic analysis.
• Plasma and aqueous humor concentrations of flurbiprofen were measured over time.

Main Results:

• Flurbiprofen disposition followed a biexponential pattern with rapid distribution in both systemic and ocular compartments.
• Plasma and aqueous humor elimination half-lives were 74 min and 93 min, respectively.
• Topical administration showed dose-dependent ocular bioavailability, with lower doses yielding higher bioavailability fractions.

Conclusions:

• Aqueous humor drainage appears to be the primary mechanism for flurbiprofen elimination from the eye.
• Systemic absorption of topically applied flurbiprofen is significant.
• The study provides valuable insights into the pharmacokinetics of NSAIDs in the eye, informing future drug development and dosing strategies.