In vivo pharmacokinetics and in vitro pharmacodynamics of nepafenac, amfenac, ketorolac, and bromfenac
Accepted 22 May 2007.
Purpose
To evaluate the aqueous humor concentrations and cyclooxygenase (COX) inhibitory activities of nepafenac, amfenac, ketorolac, and bromfenac after topical ocular administration of Nevanac (nepafenac 0.1%), Acular LS (ketorolac 0.4%), or Xibrom (bromfenac 0.09%).
Setting
Five private ophthalmology practices throughout the United States.
Methods
Patients requiring cataract extraction were randomized to 1 of 3 treatment groups: Nevanac, Acular LS, or Xibrom. Patients were administered 1 drop of the test drug 30, 60, 120, 180, or 240 minutes before cataract surgery. At the time of paracentesis, an aqueous humor sample was collected and later analyzed for drug concentration. In addition, COX-1 (homeostatic) and COX-2 (inducible) inhibitory activities of nepafenac, amfenac, ketorolac, and bromfenac were determined via the in vitro measurement of prostaglandin E2 (PGE2) inhibition.
Results
Seventy-five patients participated in the study. The prodrug nepafenac had the shortest time to peak concentration and the greatest peak aqueous humor concentration (Cmax). The Cmax of nepafenac was significantly higher than that of the other drugs (P<.05), including the higher-concentration ketorolac (0.4%). The area under the curve (AUC) of nepafenac was significantly higher (P<.05) than the AUCs of amfenac, ketorolac, and bromfenac. The combined AUCs of nepafenac and amfenac were the highest of all drugs tested (P<.05). Ketorolac showed the most potent COX-1 inhibition, whereas amfenac was the most potent COX-2 inhibitor. The PGE2 aqueous humor levels of each study medication were highly variable; as a result, meaningful interpretation of the data was not possible.
Conclusion
Nepafenac showed significantly greater ocular bioavailability and amfenac demonstrated greater potency at COX-2 inhibition than ketorolac or bromfenac.
From Keystone Research (Walters), Austin, Texas, private practices, Nacogdoches, Texas (Lehmann), Boston, Massachusetts (Raizman), and Warner Robins, Georgia (Gayton), and a surgical center (Ernest), Jackson, Michigan, USA
Corresponding author: Tom Walters, MD, Keystone Research, Department of Ophthalmology, 1020 West 34th Street, Austin, Texas 78705, USA.
Dr. Raizman is a consultant to Alcon Laboratories, Inc. Drs. Walters, Ernest, Gayton, and Lehmann have received gifts in kind, honoraria, or travel reimbursement valued at over $1000 from Alcon Laboratories, Inc., in the past 12 months. No author has a financial or proprietary interest in any material or method mentioned.
Financial support from Alcon Laboratories, Inc., Fort Worth, Texas, USA.
ABSTRACT