Hydraulic flow and vascular clearance influences on intravitreal drug delivery.
OBJECTIVE
A recent paper proposed a model for hydraulic flow inthe eye, claiming this could affect intravitreal drug administration. The impact of flow on various modes of administration was investigated in a physiologically accurate ocular model of the rabbit eye.


METHODS
Hydraulic flow initiated at the hyaloid was simulated in a three-dimensional finite element model including effects of convection and episcleral efflux. The interrelation between hydraulic and vascular clearance was treated using a method in which choroidal clearance is effected by simple boundary conditions, diminishing computing requirements. Drug diffusion coefficient and clearance rates for the choroid and anterior chamber were varied.


RESULTS
Volumes and velocities of fluid flow permeating the vitreous agreed with literature values. Hydraulic flow impacted clearance of compounds not eliminated by the choroid; agreement with experimental data justified assuming perfect aqueous humor mixing. Hypertensive pressure produced up to a maximum 4-fold change in vitreal drug content from an intravitreal device depending upon location, orientation of the releasing surface, but was less important than vascular clearance strength and diffusion coefficient.


CONCLUSIONS
The influence of intraocular pressure ([OP)-induced hydraulic flow is not likely to be of clinical significance for low molecular weight drugs that are efficiently cleared by the choroid.
Missel
Paul J
PJ
R2-45, Drug Delivery, Alcon Research Ltd., 6201 South Freeway, Fort Worth, Texas 76134, USA. paul.missel@alconlabs.com
D001783:Blood Flow Velocity / Q000187:drug effects / Q000502:physiology; D016503:Drug Delivery Systems / Q000379:methods*; D008657:Metabolic Clearance Rate / Q000187:drug effects / Q000502:physiology; D008954:Models, Biological; D014822:Vitreous Body / Q000098:blood supply* / Q000187:drug effects / Q000378:metabolism*