Shikamura Yuko, Ohtori Akira, Tojo Kakuji
Research Laboratories, Senju Pharmaceutical Co., Ltd., Hyogo, Japan.
Chem Pharm Bull (Tokyo). 2011;59(10):1263-7. doi: 10.1248/cpb.59.1263.
The purpose of this study was to analyze drug pharmacokinetics in the posterior eye tissues after topical instillation. For the in vivo study, the concentrations of ofloxacin in rabbit ocular tissues were analyzed by high performance liquid chromatography at 1, 2, and 3 h after instillation. For the in silico simulation, the concentration distribution of ofloxacin in the eye was calculated by the ocular pharmacokinetic model based on the diffusion/partition model. The simulated profiles were then compared with the in vivo experimental findings. In the in vivo study, the drug concentration in the posterior vitreous body initially decreased with time after topical instillation, and thereafter, the concentration increased. The in silico simulation of ocular pharmacokinetics indicated that the drug penetration of the posterior vitreous body was determined by three major pathways: (1) the initial transscleral penetration, (2) the intermediate transcorneal penetration, and (3) the late transretinal penetration. The in vivo findings were well described by a series of contributions by these three pathways. In conclusion, the present in vivo and in silico studies suggest that the instilled drugs initially reached the posterior vitreous body by diffusion through the sclera and then later by corneal penetration and systemic circulation.
本研究的目的是分析局部滴注后眼后段组织中的药物药代动力学。在体内研究中，通过高效液相色谱法分析滴注后1、2和3小时兔眼组织中氧氟沙星的浓度。在计算机模拟中，基于扩散/分配模型的眼药代动力学模型计算了氧氟沙星在眼中的浓度分布。然后将模拟曲线与体内实验结果进行比较。在体内研究中，局部滴注后玻璃体后段的药物浓度最初随时间下降，此后浓度升高。眼药代动力学的计算机模拟表明，玻璃体后段的药物渗透由三个主要途径决定：（1）初始经巩膜渗透，（2）中间经角膜渗透，（3）后期经视网膜渗透。这三个途径的一系列作用很好地描述了体内研究结果。总之，目前的体内和计算机模拟研究表明，滴注的药物最初通过巩膜扩散到达玻璃体后段，然后通过角膜渗透和全身循环到达。
