Intraocular tissue plasminogen activator concentrations after subconjunctival delivery.
BACKGROUND
Topical application of recombinant tissue plasminogen activator (tPA) results in detectable intraocular tPA levels. The authors sought to determine whether subconjunctival delivery of recombinant tPA results in enhanced intraocular drug levels.


METHODS
One week after first performing a gas vitrectomy in each eye, the authors injected 0.4 ml of a tPA solution (1 or 10 mg/ml) subconjunctivally in one eye of 16 rabbits and 0.4 ml of sterile water in the fellow control eye. Vitreous taps were performed to obtain vitreous samples for measuring tPA concentrations. An anterior chamber paracentesis was then done for each concentration at 15, 30, and 60 minutes. Aqueous and vitreous tPA concentrations were determined using a two-site enzyme-linked immunosorbent assay (ELISA).


RESULTS
Vitreous tPA levels were higher than aqueous levels in the treated eyes. Vitreous levels averaged 7 +/- 7 ng/ml for the 1-mg/ml group (n = 7/7) and 202 +/- 230 ng/ml for the 10-mg/ml group (n = 7/8). Aqueous levels were positive in 8 of 16 samples. The authors conclude that subconjunctival delivery of tPA results in both vitreous and aqueous tPA levels.
Lim
J I
JI
Wilmer Ophthalmological Institute, Johns Hopkins Hospital, Baltimore.
Maguire
A M
AM
John
G
G
Mohler
M A
MA
Fiscella
R G
RG
D000818:Animals; D001082:Aqueous Humor / Q000378:metabolism*; D003228:Conjunctiva; D004797:Enzyme-Linked Immunosorbent Assay; D007267:Injections; D011817:Rabbits; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage / Q000493:pharmacokinetics*; D014821:Vitrectomy; D014822:Vitreous Body / Q000378:metabolism*
D010959:Tissue Plasminogen Activator