Aqueous prostaglandin E2 of cataract patients at trough ketorolac and bromfenac levels after 2 days dosing

Abstract

Ketorolac 0.4% administered four times daily (q.i.d.) has long been used safely and effectively for the alleviation of ocular inflamation and pain and the prevention of intraoperative miosis in patients undergoing cataract surgery. Bromfenac ophthalmic solution 0.09% was recently developed as an ocular anti-inflammatory drug with a twice-daily (b.i.d.) dosing regimen. This study was designed to evaluate if b.i.d. dosing with bromfenac 0.09%, in comparison with q.i.d. dosing with ketorolac 0.4%, provides adequate trough nonsteroidal anti-inflammatory drug levels that were effective enough to reduce aqueous prostaglandin (PG) E(2) levels of patients after cataract surgery toward the end of its dosing cycle. In this single-center, investigator-masked trial, patients undergoing cataract surgery were randomized to receive either ketorolac 0.4% q.i.d. or bromfenac 0.09% b.i.d. for 2 days preoperatively. Aqueous humor was collected at the start of surgery 6 hours after the last dose of ketorolac 0.4% and 12 hours after the last dose of bromfenac 0.09%. Aqueous PGE(2) levels and drug concentrations were evaluated by a competitive enzyme immunoassay and reverse-phase HPLC-mass spectroscopy, respectively. A total of 61 patients received ketorolac 0.4% (n=30) or bromfenac 0.09% (n=31). The mean (+/-SD) aqueous PGE(2) level was 285.6+/-141.9 pg/mL in patients treated with ketorolac 0.4% and 386.2+/-131.0 pg/mL in patients treated with bromfenac 0.09% (P=0.006). The mean (+/-SD) aqueous concentrations of ketorolac and bromfenac were 83.6+/-73.8 ng/mL and 9.2+/-6.6 ng/mL, respectively (P<0.001). Ketorolac 0.4% maintained significantly higher aqueous concentrations and lowered aqueous PGE(2) levels significantly more than bromfenac 0.09% at trough levels. Ketorolac 0.4% administered q.i.d. may provide a more sustained control of intraocular inflammation and pain than bromfenac 0.09% administered b.i.d.