Tojo K J, Ohtori A
Department of Biochemical Engineering and Science, Kyushu Institute of Technology, Fukuoka, Japan.
Math Biosci. 1994 Sep;123(1):59-75. doi: 10.1016/0025-5564(94)90018-3.
A dynamic mathematical model is developed to describe the distribution and elimination behavior of a drug in the vitreous body following intravitreal injection. The effects of three elimination pathways--the annular gap between the lens and the ciliary body (the posterior chamber), the lens, and the retina-choroid-sclera membrane--upon the concentration distribution in the vitreous body and the time course of the rate of elimination have been quantitatively demonstrated. The effects of metabolism in the vitreous body and the site of injection are also simulated. The annular gap between the lens and the ciliary body (the posterior chamber) is found to be a main route of elimination for large molecules injected into the vitreous body. For small or highly lipophilic molecules, however, both the posterior chamber and the retina-choroid-sclera membrane act as major routes of elimination. The lens pathway may contribute negligibly to the escape of drugs from the vitreous body. The concentration on the surface of the retina is appreciably affected by the site of injection or the initial distribution profiles, while the concentration gradient on the lens surface remains almost independent of the site of injection. To maintain the therapeutic concentration in the vitreous body or in the retina for a prolonged period of time, the drug must be injected into the posterior area of the vitreous body. When the drug is injected into the anterior segment of the vitreous body, the drug molecules quickly escape into the posterior chamber from the annular gap between the lens and the ciliary body. The present mathematical model describes well in vivo elimination profile of lomefloxacin following intravitreal injection.
建立了一个动态数学模型，以描述玻璃体内注射药物后在玻璃体中的分布和消除行为。定量证明了三种消除途径——晶状体与睫状体之间的环形间隙（后房）、晶状体以及视网膜-脉络膜-巩膜膜——对玻璃体内浓度分布和消除速率时间进程的影响。还模拟了玻璃体中的代谢作用和注射部位的影响。发现晶状体与睫状体之间的环形间隙（后房）是注入玻璃体的大分子的主要消除途径。然而，对于小分子或高度亲脂性分子，后房和视网膜-脉络膜-巩膜膜均为主要消除途径。晶状体途径对药物从玻璃体中逸出的作用可能微不足道。视网膜表面的浓度受注射部位或初始分布曲线的显著影响，而晶状体表面的浓度梯度几乎与注射部位无关。为了在玻璃体或视网膜中长时间维持治疗浓度，必须将药物注入玻璃体的后部区域。当药物注入玻璃体前段时，药物分子会从晶状体与睫状体之间的环形间隙迅速逸入后房。本数学模型很好地描述了玻璃体内注射洛美沙星的体内消除情况。
