Ocular pharmacokinetics of a single dose of bromfenac sodium ophthalmic solution 0.1% in human aqueous humor.

Abstract

PURPOSE:

The aim of this study was to evaluate the ocular pharmacokinetics of a single dose of bromfenac sodium ophthalmic solution 0.1% in subjects undergoing routine cataract surgery with intraocular lens implantation.

METHODS:

An open-label, phase II confirmatory study of 54 subjects undergoing cataract surgery with intraocular lens implantation. A single drop of bromfenac sodium ophthalmic solution 0.1% was administered at 30, 60, 90, 120, 180, or 240 min prior to the initiation of cataract surgery. Samples of aqueous humor were aspirated through a paracentesis and analyzed by using high-performance liquid chromatography. Based upon these data, predicted concentrations of bromfenac in the aqueous humor over 24 h were generated by using computer simulation and compared with the IC(50) for bromfenac as a measure of anti-inflammatory efficacy.

RESULTS:

Peak aqueous-humor concentrations of bromfenac occurred between 150 and 180 min following ophthalmic dosing, with a mean concentration of 78.7 ng/mL. The level of bromfenac decreased in a log-linear fashion with an elimination-rate constant of 1.4. Bromfenac remained above the IC(50) value of cyclo-oxygenase-2 (COX-2) during the evaluated time points and over the 12-h dosing interval, using a computer model of extrapolated time points and assuming first-order elimination.

CONCLUSIONS:

Pharmacokinetic modeling, based upon samples collected over 240 min after a single dose of bromfenac sodium ophthalmic solution 0.1% suggests that aqueous-humor concentrations remain at clinically effective levels (above its IC(50) value for COX-2) for over 12 h. Based upon this rationale, these results supported clinical trials that demonstrated the efficacy of twice-daily dosing of bromfenac sodium ophthalmic solution 0.1% to manage patients with postoperative ocular pain and inflammation.

• Authors: Kensaku Miyake, Takahiro Ogawa, Tetsuya Tajika, James A Gow, Timothy R McNamara
• Journal: Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics (J Ocul Pharmacol Ther) Vol. 24 Issue 6 Pg. 573-8 (Dec 2008) ISSN: 1557-7732 [Electronic] United States
• PMID: 19049295 (Publication Type: Clinical Trial, Phase II, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Inflammatory Agents, Non-Steroidal
• Benzophenones
• Bromobenzenes
• bromfenac

Topics

• Adult
• Aged
• Aged, 80 and over
• Anti-Inflammatory Agents, Non-Steroidal (pharmacokinetics)
• Aqueous Humor (metabolism)
• Benzophenones (pharmacokinetics)
• Bromobenzenes (pharmacokinetics)
• Female
• Humans
• Male
• Middle Aged