title: 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.
authors: Bucci Laser Vision Institute, Wilkes-Barre, PA 18702, USA. buccivision@aol.com
authors: Frank A
authors: FA
authors: Bucci
authors: L David
authors: LD
authors: Waterbury
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000493:pharmacokinetics*; D044482:Benzeneacetamides / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001577:Benzophenones / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001969:Bromobenzenes / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002386:Cataract / Q000188:drug therapy* / Q000378:metabolism; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D020910:Ketorolac / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D010648:Phenylacetates / Q000008:administration & dosage / Q000493:pharmacokinetics*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D044482:Benzeneacetamides; D001577:Benzophenones; D001969:Bromobenzenes; D010648:Phenylacetates; C414203:nepafenac; C053083:bromfenac; D020910:Ketorolac