PHARMACOKINETIC ANALYSIS FOR ADEQUATE MEDICATION-USE IN OPHTHALMOLOGY

本研究的目的是建立眼部给药后药物在眼内分布的药代动力学模型。(1)使用双室玻璃扩散池测量各种药物穿过白化病兔的离体眼膜的渗透。作为结果，所获得的渗透剖面进行了分析的基础上的无限剂量系统的扩散模型。(2)用数学模型描述了滴注后药物在兔角膜前区的分布和注入眼房后药物在兔眼房水中的分布。这些处置取决于药物的亲脂性和分子量。(3)在此基础上，建立了含扩散过程的药物眼内分布的房室模型。该动力学模型很好地描述了在麻醉兔中滴注后房水中的药物浓度， ...更多信息 用作泪液分泌不足的模型。这些结果表明了动力学模型的正确性。(4)为了扩大该动力学模型的应用范围，采用该动力学模型分析了粘性载体、聚合物插入物、亲脂性前药和促吸收制剂给药后药物在兔眼内的分布情况。基于包括扩散过程的改进模型的模拟很好地描述了药物以粘性载体和聚合物插入物的形式应用后的房水浓度。以亲脂性前药和促吸收制剂的形式应用后，通过动力学模型估计药物的表观渗透参数。(5)利用已有的人体实验数据建立了眼部给药的动力学模型和参数，为眼部给药系统的开发和合理用药方案的制定提供了依据。少

Purpose of this research is to develop the pharmacokinetic model for drug disposition in the eye after ocular application.(1) The penetrations of various drugs were measured across the isolated ocular membranes of the albino rabbit using a two-chamber glass diffusion cell. As the results, the obtained penetration profiles were analyzed based on a diffusion model for the infinite dose system.(2) The drug dispositions in the precorneal area of the rabbits after instillation and the drug dispositions in the aqueous humor of rabbits after injection into the aqueous chamber of the eye were characterized by mathematical model. These dispositions were dependent on drug lipophilicity and molecular weight.(3) On the basis of these results, the compartment model including the diffusion process was developed to describe the drug dispositions in the eye after instillation. The kinetic model well described the drug concentrations in the aqueous humor after instillation in anesthetized rabbits that … More was used as a model of tear secretion deficiency. These results indicated the propriety of the kinetic model.(4) In order to expand the application of the kinetic model, the drug dispositions in the eye of rabbits were analyzed using the kinetic model after application in the form of viscous vehicle, polymeric insert, lipophilic prodrug, and absorption promoting formulation. The simulation based on the modified model including the diffusion process well described the aqueous humor concentration of drugs after application in the form of viscous vehicle and polymeric insert. The apparent permeability parameters of drugs were estimated by the kinetic model after application in the form of lipophilic prodrug and absorption promoting formulation.(5) The kinetic model and the parameters for human were developed using human data previously reported.Thus, the kinetic model and parameters are effective to develop the ocular drug delivery systems and estimate the adequate regimen for ophthalmic medication. Less