Determination of vitreous, aqueous, and plasma concentration of orally administered voriconazole in humans.
OBJECTIVE
To investigate the penetration of voriconazole, a new-generation triazole antifungal agent, into the vitreous and aqueous humor after oral administration.


METHODS
A prospective, nonrandomized clinical study included 14 patients scheduled for elective pars plana vitrectomy surgery between December 1, 2002, and February 28, 2003, at the Cullen Eye Institute, Houston, Tex. Aqueous, vitreous, and plasma samples were obtained and analyzed from 14 patients after oral administration of two 400-mg doses of voriconazole taken 12 hours apart before surgery. Assays were performed by means of high-performance liquid chromatography.


RESULTS
Mean +/- SD voriconazole concentrations in plasma (n = 14), vitreous (n = 14), and aqueous (n = 11) were 2.13 +/- 0.93 microg/mL, 0.81 +/- 0.31 microg/mL, and 1.13 +/- 0.57 microg/mL, respectively. Mean +/- SD sampling times after oral administration of the second voriconazole dose for plasma, vitreous, and aqueous were 2.4 +/- 0.6 hours, 3.0 +/- 0.5 hours, and 2.9 +/- 0.5 hours, respectively. The percentages of plasma voriconazole concentration achieved in the vitreous and aqueous were 38.1% and 53.0%, respectively. Mean vitreous and aqueous minimum inhibitory concentrations for 90% of isolates (MIC(90)) were achieved against a wide spectrum of yeasts and molds, including Aspergillus species and Candida species, along with many other organisms.


CONCLUSIONS
Orally administered voriconazole achieves therapeutic aqueous and vitreous levels in the noninflamed human eye, and the activity spectrum appears to appropriately encompass the most frequently encountered mycotic species involved in the various causes of fungal endophthalmitis. Because of its broad spectrum of coverage, low MIC(90) levels for the organisms of concern, good tolerability, and excellent bioavailability with oral administration, it may represent a major advance in the prophylaxis or management of exogenous or endogenous fungal endophthalmitis.
Hariprasad
Seenu M
SM
Barnes Retina Institute, Washington University School of Medicine, St Louis, MO, USA.
Mieler
William F
WF
Holz
Eric R
ER
Gao
Hua
H
Kim
Judy E
JE
Chi
Jingduan
J
Prince
Randall A
RA
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000935:Antifungal Agents / Q000493:pharmacokinetics*; D001082:Aqueous Humor / Q000378:metabolism*; D001682:Biological Availability; D001692:Biological Transport; D002851:Chromatography, High Pressure Liquid; D005260:Female; D005658:Fungi / Q000187:drug effects; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D011446:Prospective Studies; D011743:Pyrimidines / Q000493:pharmacokinetics*; D014230:Triazoles / Q000493:pharmacokinetics*; D014821:Vitrectomy; D014822:Vitreous Body / Q000378:metabolism*; D065819:Voriconazole
D000935:Antifungal Agents; D011743:Pyrimidines; D014230:Triazoles; D065819:Voriconazole