A Double-Masked, Randomized, Single-Dose, Pharmacokinetic Study of Nepafenac, Amfenac, Ketorolac, and Bromfenac in Human Aqueous Humor Following Topical Administration of NevanacTM, Acular LSTM, or XibromTM

Abstract

Purpose:: To evaluate the aqueous humor concentrations of nepafenac, amfenac, ketorolac, and bromfenac following topical administration of Nevanac, Acular LS, or Xibrom

Methods:: Patients who were at least 18 years of age, of any race and either gender, and requiring cataract extraction with planned IOL implantation were randomized to 1 of 3 treatments consisting of either 1 drop of Nevanac, Acular LS, or Xibrom prior to cataract surgery. Patients were administered the test article at 30, 60, 120, 180, or 240 minutes before cataract surgery. At the time of paracentesis, the aqueous humor sample was collected (approximately 0.15 mL) from the study eye. Each sample was analyzed for drug concentration and AUC_0-4h was calculated for each drug.

Results:: Seventy-five patients participated in the study. Nepafenac had the fastest t_max (30 min), followed by ketorolac (60 min), amfenac (180 min), and bromfenac (240 min). Nepafenac had the highest C_max (205.3 ± 101.7 ng/ml), followed by amfenac (70.1 ± 20.1 ng/ml), ketorolac (57.5 ± 38.8 ng/ml), and bromfenac (23.9 ± 3.9 ng/ml). The C_max for nepafenac was significantly higher than that of all the other drugs (p<0.05); the C_max for bromfenac was significantly lower than nepafenac (p=0.0162) and amfenac (p=0.0058), and similar to ketorolac (p=0.1250). The AUC for nepafenac (331.1 ng h/ml) was significantly higher (p<0.05) than the AUCs of amfenac, ketorolac, and bromfenac (178.1, 176.9, and 49.2 ng h/ml, respectively). The AUCs of amfenac and ketorolac were significantly higher than that of bromfenac (p<0.05). The combined AUCs of nepafenac and amfenac yielded the highest AUC compared to all products (487.5 ng h/ml, p<0.05).

Conclusions:: Nevanac demonstrated a significantly greater ocular bioavailability of drug than either Acular LS or Xibrom, suggesting that differences in efficacy may exist among these 3 agents for the prevention and treatment of anterior chamber inflammation following cataract surgery.

Clinical Trial:: www.clinicaltrials.gov pending

Keywords: cataract • inflammation • metabolism