Missel Paul J
R2-45, Drug Delivery, Alcon Research Ltd., 6201 South Freeway, Fort Worth, Texas 76134, USA.
Pharm Res. 2002 Nov;19(11):1636-47. doi: 10.1023/a:1020940927675.
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.
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.
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.
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.
最近一篇论文提出了一种眼内液流模型，声称其可能影响玻璃体内药物给药。在生理上精确的兔眼模型中研究了液流对各种给药方式的影响。
在一个三维有限元模型中模拟了始于玻璃体的液流，该模型包括对流和巩膜外流的影响。采用一种通过简单边界条件影响脉络膜清除率的方法来处理液流与血管清除之间的相互关系，从而降低计算要求。改变药物扩散系数以及脉络膜和前房的清除率。
渗透到玻璃体中的流体体积和速度与文献值一致。液流影响未被脉络膜清除的化合物的清除；与实验数据的一致性证明了假设房水完全混合是合理的。高血压压力根据释放表面的位置、方向，使玻璃体内装置中的玻璃体药物含量最多产生4倍的变化，但比血管清除强度和扩散系数的影响小。
对于能被脉络膜有效清除的低分子量药物，眼压（IOP）诱导的液流影响不太可能具有临床意义。
