Corneal penetration of diclofenac from a fixed combination of diclofenac-gentamicin eyedrops.
OBJECTIVE
To establish the corneal penetration of diclofenac in the presence of gentamicin in patients having cataract surgery.


METHODS
Kantonsspital Augenklinik, Aarau, and Hôpital 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.


CONCLUSIONS
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.
Killer
H E
HE
CIBA Vision AG, Bülach, Switzerland.
Borruat
F X
FX
Blumer
B K
BK
Herbort
C P
CP
Jauch
A
A
D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001082:Aqueous Humor / Q000378:metabolism; D002387:Cataract Extraction; D002851:Chromatography, High Pressure Liquid; D003315:Cornea / Q000378:metabolism*; D004008:Diclofenac / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004359:Drug Therapy, Combination; D005260:Female; D005839:Gentamicins / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006801:Humans; D008297:Male; D009883:Ophthalmic Solutions
D000900:Anti-Bacterial Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D005839:Gentamicins; D009883:Ophthalmic Solutions; D004008:Diclofenac