A randomized comparison of to-aqueous penetration of ketorolac 0.45%, bromfenac 0.09% and nepafenac 0.1% in cataract patients undergoing phacoemulsification

Abstract

Objective:

To compare the peak to-aqueous penetration of three nonsteroidal anti-inflammatory drugs: ketorolac tromethamine 0.45%, bromfenac 0.09%, nepafenac 0.1%, and amfenac (the active metabolite of nepafenac) in patients undergoing phacoemulsification.

Methods:

A single center, double-masked study randomized 122 patients to receive one of three treatment arms. On-label dosing of ketorolac (BID), bromfenac (BID), and nepafenac (TID) was instructed for 1 day prior to surgery. Patients were instructed to instill one drop the morning of surgery. The patients received four additional doses 1 hour prior to phacoemulsification. After completion of the paracentesis site with a superblade, aqueous humor (0.15 cc) was collected through the peripheral clear cornea with a 30-gauge needle attached to a TB syringe. Following collection, aqueous samples were stored at −40°C prior to analysis. Drug concentrations were analyzed by liquid chromatography tandem mass spectrometry using positive turbo-ion spray ionization and multiple reaction monitoring mode for quantification. An independent sample Student’s t-test was used to detect between-group differences.

Results:

The peak aqueous concentration of ketorolac 0.45% was 10 times the concentration of bromfenac 0.09%, and five times the concentration of and 54% greater than the metabolically inactive nepafenac 0.1%. The mean peak aqueous concentration of ketorolac 0.45% was 688.87 ± 749.6 ng/ml. Bromfenac achieved a mean peak aqueous concentration of 67.64 ± 62.4 ng/ml. The mean peak aqueous concentrations of nepafenac and amfenac were 447.10 ± 225.7 ng/ml and 140.37 ± 56.6 ng/ml, respectively. The peak concentration of ketorolac was statistically significantly greater than bromfenac (P ≤ 0.0005), nepafenac (P ≤ 0.05), and amfenac (P ≤ 0.005). A limitation of this study is that aqueous samples were collected just prior to surgery and not during the postoperative period due to ethical considerations.

Conclusions:

Ketorolac 0.45% achieved significantly greater aqueous concentrations when compared to bromfenac 0.09% and the active metabolite of nepafenac 0.1% (amfenac) in patients undergoing phacoemulsification.

Trial registration: ClinicalTrials.gov identifier: NCT01001806.

Key words::

• Amfenac
• Aqueous penetration
• Bromfenac
• Ketorolac
• Nepafenac

Transparency

Declaration of funding

This study was funded by an unrestricted educational grant from Allergan.

Declaration of financial/other relationships

F.A.B. and L.D.W. are consultants for Allergan, Inc.

CMRO peer reviewers may have received honoraria for their review work. The peer reviewers on this manuscript have disclosed that they have no relevant financial relationships.

Acknowledgments

This information was first presented as a poster at the Association for Research in Vision and Ophthalmology, Fort Lauderdale, FL, USA, May 1–6, 2010. Statistics were performed by Double Precision Consulting of Albany, NY, USA.