Ocular pharmacokinetics of a single dose of bromfenac sodium ophthalmic solution 0.1% in human aqueous humor.
OBJECTIVE
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.
Miyake
Kensaku
K
Shozankai Medical Foundation of the Miyake Eye Hospital, Nagoya, Japan.
Ogawa
Takahiro
T
Tajika
Tetsuya
T
Gow
James A
JA
McNamara
Timothy R
TR
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000493:pharmacokinetics*; D001082:Aqueous Humor / Q000378:metabolism*; D001577:Benzophenones / Q000493:pharmacokinetics*; D001969:Bromobenzenes / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001577:Benzophenones; D001969:Bromobenzenes; C053083:bromfenac