Pharmacokinetics of intraocular drug delivery of Oregon green 488-labeled triamcinolone by subtenon injection using ocular fluorophotometry in rabbit eyes.
OBJECTIVE
To evaluate the transscleral delivery of Oregon Green-labeled triamcinolone acetonide (OGTA) into the eye.


METHODS
Ex vivo experiments were performed on rabbit sclera in a Lucite block perfusion chamber. Two hundred microliters OGTA (5 mg/mL) was placed on the outer surface of the sclera for 24 hours. The exposed sclera was divided into two pieces; one half for a washout of OGTA and the other for histology. The concentration of OGTA that diffused through the sclera (n = 6) was measured by fluorometry. Two hundred microliters of OGTA (5 mg/mL) was also injected subtenon into live (n = 6) and euthanatized rabbits (n = 3). Intraocular OGTA concentrations were measured by ocular fluorophotometry.


RESULTS
The permeability constant for the transscleral diffusion (K(trans)) of OGTA was 1.12 x 10(-7) +/- 0.08 cm/s (n = 8) during the steady state perfusion. Washout tests showed higher OGTA concentration in the sclera exposed to OGTA for 4 hours than in that exposed for 1 hour. Fluorescent microscopy showed OGTA fluorescence throughout the exposed sclera, as evidence of scleral penetration of OGTA. The maximum OGTA concentration in the retina/choroid after subtenon injection was 25.77 +/- 10.26 ng/mL in the live rabbit at 3 hours and 84.68 +/- 21.04 ng/mL in the euthanatized rabbits at 8 hours.


CONCLUSIONS
OGTA is capable of diffusing across isolated rabbit sclera ex vivo and into the retina/choroid via transscleral diffusion from a subtenon depot in vivo. Conjunctival and choroidal circulation decreased the drug delivery of OGTA.
Lee
Sung Jin
SJ
Department of Ophthalmology, College of Medicine, Soonchunhyang University, Seoul, Korea.
Kim
Esther S
ES
Geroski
Dayle H
DH
McCarey
Bernard E
BE
Edelhauser
Henry F
HF
D000818:Animals; D000869:Anterior Eye Segment / Q000378:metabolism; D002264:Carboxylic Acids / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002829:Choroid / Q000378:metabolism; D003238:Connective Tissue; D016503:Drug Delivery Systems; D005456:Fluorescent Dyes / Q000008:administration & dosage / Q000493:pharmacokinetics*; D015590:Fluorophotometry / Q000379:methods*; D005938:Glucocorticoids / Q000008:administration & dosage / Q000493:pharmacokinetics*; D007267:Injections; D008856:Microscopy, Fluorescence; D010539:Permeability; D011817:Rabbits; D012160:Retina / Q000378:metabolism; D012590:Sclera / Q000378:metabolism*; D014222:Triamcinolone Acetonide / Q000008:administration & dosage / Q000493:pharmacokinetics*; D014822:Vitreous Body / Q000378:metabolism
D002264:Carboxylic Acids; D005456:Fluorescent Dyes; D005938:Glucocorticoids; C436864:Oregon Green 488 carboxylic acid; D014222:Triamcinolone Acetonide