Corneal penetration of diclofenac from a fixed combination of diclofenac-gentamicin eyedrops

Abstract

Purpose: To establish the corneal penetration of diclofenac in the presence of gentamicin in patients having cataract surgery.Setting: Kantonsspital Augenklinik, Aarau, and H6pital Jules Gonin, Lausanne, Switzerland.Methods: Eligible patients having cataract surgery (39 women, 30 men) were treated with 4 drops of diclofenac 0.1 %-gentamicin 0.3% (Voltamicin®) instilled at 20 minute intervals. Paracentesis was performed 15, 30, or 60 minutes after the last instillation, and a sample of aqueous humor was collected for analysis of diclofenac by high-performance liquid chromatography. Blood samples of some patients were obtained before surgery for analysis.Results: Mean diclofenac levels (±SD) in the aqueous humor 15, 30, and 60 minutes after the last instillation were 72 ± 84, 108 ± 87, and 201 ± 116 ng/mL (= 682 nMol/L), respectively. Diclofenac remained below the limit of detection (5 ng/mL) in all samples of blood serum. In general, local tolerance was good; no side effects were reported. Comparison of the data with published results of topically instilled diclofenac 0.1% suggests that the concentration of diclofenac in the aqueous humor achieved with 4 instillations of the combination product is similar to that achieved with 8 instillations of diclofenac 0.1% (Voltaren Ophtha®) alone.Conclusion: Drug levels of diclofenac in the aqueous humor well above IC-50 for cyclo-oxygenase were achieved with the regimen applied. No inhibitory effect by the gentamicin or vehicle was observed. Comparison of these data with published results of Voltaren Ophtha implies a 2-fold better penetration of diclofenac with the diclofenac-gentamicin combination.