Comparison of voriconazole concentration in the aqueous humor and vitreous between non-scraped and scraped corneal epithelium groups after topical 1% voriconazole application.
OBJECTIVE
To investigate the penetration of topical 1% voriconazole through the cornea into the aqueous humor in New Zealand white rabbits and to determine the effect of mechanical scraping of the corneal epithelium.


METHODS
The right eyes of 29 New Zealand white rabbits were maintained with the epithelium intact, and the left eyes underwent mechanical epithelium debridement of the central 7.5 mm of the cornea. A loading dose consisted of a drop of 1% voriconazole applied every 5 min for the initial half hour and followed by a maintenance dose consisting of a drop every 20 min, which was applied for about 2 hr. Then, the first sample was obtained 5 min after the first seven doses (loading dose) were given, and then four more samples were taken 5 min after four more subsequent drops (maintenance dose). The samples were analyzed by high performance liquid chromatography.


RESULTS
The mean aqueous concentration of voriconazole was 33.44 +/- 5.77 microg/mL 5 min after the loading dose in the non-scraped group and 57.67 +/- 6.77 microg/mL in the scraped group, respectively. The mean aqueous concentration of voriconazole was maintained in a range from 19.97 to 23.70 microg/mL 5 min after the maintenance doses in the non-scraped group and from 44.44 to 49.02 microg/ mL in the scraped group. The mean vitreous concentration of voriconazole ranged from 0.38 to 0.49 microg/mL in the non-scraped group and ranged from 0.72 to 0.94 microg/mL in the scraped group. These levels were statistically significant (P < 0.05) between the scraped and non-scraped groups.


CONCLUSIONS
Topically administered voriconazole achieved minimum inhibitory concentrations in the aqueous for all the organisms most commonly involved in fungal endophthalmitis and achieved minimum inhibitory concentrations in the vitreous for some pathogenic fungi. The concentrations of voriconazole were higher in the scraped group than in the non-scraped group.
Wei
Li-Chen
LC
Department of Ophthalmology, Taichung Veterans General Hospital, Taiwan, ROC.
Tsai
Tsun-Chung
TC
Tsai
Hin-Yeung
HY
Wang
Chun-Yuan
CY
Shen
Ying-Cheng
YC
D000287:Administration, Topical; D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001082:Aqueous Humor / Q000378:metabolism*; D001682:Biological Availability; D001692:Biological Transport; D002851:Chromatography, High Pressure Liquid; D003646:Debridement; D019573:Epithelium, Corneal / Q000378:metabolism* / Q000601:surgery; D008826:Microbial Sensitivity Tests; D009883:Ophthalmic Solutions / Q000008:administration & dosage / Q000493:pharmacokinetics; D011743:Pyrimidines / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011817:Rabbits; D014230:Triazoles / Q000008:administration & dosage / Q000493:pharmacokinetics*; D014822:Vitreous Body / Q000378:metabolism*; D065819:Voriconazole
D000935:Antifungal Agents; D009883:Ophthalmic Solutions; D011743:Pyrimidines; D014230:Triazoles; D065819:Voriconazole