Vitreous and Aqueous Penetration of Orally Administered Trimethoprim-Sulfamethoxazole Combination in Humans.
OBJECTIVE
To determine the penetration of orally administered trimethoprim (TMP)-sulfamethoxazole (SMX) into the aqueous and vitreous cavity of noninflamed human eyes.


METHODS
Nine adult patients undergoing cataract surgery and 10 adult patients undergoing pars plana vitrectomy were given 3 doses of oral TMP-SMX every 12 hours before the surgery. Aqueous and blood samples were collected from patients undergoing cataract surgery; vitreous and blood samples were collected from patients undergoing vitrectomy. The levels of TMP and SMX were analyzed using high-performance liquid chromatography and were compared with the mean minimum inhibitory concentrations (MIC) of potential ocular pathogens.


RESULTS
TMP-SMX was present in all samples. Among eyes undergoing cataract surgery, the mean concentrations of TMP in aqueous and blood were 0.341 ± 0.141 μg/mL (mean ± SD) and 1.501 ± 0.433 μg/mL and of SMX were 5.259 ± 0.929 μg/mL and 11.835 ± 2.100 μg/mL, respectively. Among eyes undergoing vitrectomy, the mean concentrations of TMP in vitreous and blood were 1.864 ± 0.807 μg/mL and 4.591 ± 2.979 μg/mL and of SMX were 5.910 ± 2.705 μg/mL and 39.289 ± 15.469 μg/mL, respectively. MIC levels were achieved against many bacterial pathogens, including methicillin-resistant Staphylococcus aureus.


CONCLUSIONS
TMP-SMX penetrates both the aqueous and vitreous cavities when given orally. The components reach therapeutic inhibitory concentrations in the ocular cavity against many potential pathogens.
*Department of Ophthalmology, University of California, Davis Medical Center, Sacramento, CA; †Department of Ophthalmology, University of Texas Health Science Center at San Antonio, San Antonio, TX; ‡Department of Pathology and Laboratory Medicine, University of California, Davis Medical Center, Sacramento, CA; and §Department of Ophthalmology and Visual Sciences, John A. Moran Eye Center, University of Utah, Salt Lake City, UT.
Vahid
V
Feiz
Lisa
L
Nijm
Randolph D
RD
Glickman
Lawrence S
LS
Morse
David G
DG
Telander
Susanna S
SS
Park
Christopher R
CR
Polage
Steven M
SM
Christiansen
Majid
M
Moshirfar
D000284:Administration, Oral; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics*; D001082:Aqueous Humor / Q000378:metabolism*; D001419:Bacteria / Q000187:drug effects; D001682:Biological Availability; D002387:Cataract Extraction; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D014018:Tissue Distribution; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000493:pharmacokinetics*; D014821:Vitrectomy; D014822:Vitreous Body / Q000378:metabolism*
D000900:Anti-Bacterial Agents; D015662:Trimethoprim, Sulfamethoxazole Drug Combination