>Purpose: To determine the ocular toxicity, systemic exposure, and amounts of dexamethasone sodium phosphate (DSP) in ocular tissues after administration of DSP with the Visulex system (DSP-Visulex).>Methods: DSP-Visulex was applied onto healthy rabbit eyes. DSP concentrations (4%, 8%, 15%, and 25%) and treatment durations (5, 10, and 20 min) were evaluated for the amounts of DSP in the ocular tissues and in plasma after single administrations of DSP-Visulex. The drug in eye tissues and plasma was analyzed by high-performance liquid chromatography-UV/VIS and by liquid chromatography–mass spectrometry, respectively. The safety and tolerability were ascertained based on clinical observations and histopathological examinations from repeat weekly DSP-Visulex treatments (4%, 8%, 15%, and 25% for 20 min) for 12 weeks.>Results: Significant amounts of DSP (ie, higher than 1 μg/g) were found in the anterior chamber, retina-choroid, cornea, vitreous, conjunctiva, and sclera after single applications of DSP-Visulex. The DSP concentrations in the ocular tissues and in plasma increased with increased DSP concentrations in the Visulex applicator and with increased application times. Systemic DSP was rapidly detected. The plasma half-life was 2–3 h. Cmax was 148 and 1,844 ng/mL, and the area under the plasma drug concentration versus time curve (AUC) was 418 and 3,779 ng · h/mL for the low dose (4% DSP-Visulex for 5 min) and the high dose (15% DSP-Visulex for 20 min), respectively. Ocular findings over 12 weeks were mostly conjunctival injection and eye discharge. These were transient and mild. Histopathological examinations indicated the eyes to be normal.>Conclusions: DSP can be administered safely and effectively into the rabbit eye with the Visulex system. Treatment duration and DSP concentration are important factors in achieving therapeutic levels. Repeat applications of DSP-Visulex are safe and well tolerated for weekly administrations over 4–12 weeks. DSP-Visulex has clinical potential for the noninvasive treatment of ocular diseases.
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机译：>目的：确定使用Visulex系统（DSP-Visulex）施用DSP后眼组织中的眼毒性，全身暴露以及地塞米松磷酸钠（DSP）的含量。>方法：< / strong>将DSP-Visulex应用于健康的兔子眼睛。单次施用DSP-Visulex后，评估眼组织和血浆中DSP的含量，评估DSP浓度（4％，8％，15％和25％）和治疗时间（5、10和20分钟）。分别通过高效液相色谱-UV / VIS和液相色谱-质谱法分析了眼组织和血浆中的药物。根据临床观察和每周两次重复DSP-Visulex治疗（20％分别为4％，8％，15％和25％）持续12周的组织病理学检查，确定安全性和耐受性。>结果：单次使用DSP-Visulex后，在前房，视网膜脉络膜，角膜，玻璃体，结膜和巩膜中发现大量的DSP（即高于1μg/ g）。眼组织和血浆中DSP的浓度随Visulex涂抹器中DSP浓度的增加和涂抹时间的增加而增加。快速检测到系统DSP。血浆半衰期为2–3 h。对于低剂量（4％DSP-Visulex，5分钟）和高剂量，Cmax为148和1,844 ng / mL，血浆药物浓度与时间曲线下的面积（AUC）为418和3,779 ng·h / mL （15％DSP-Visulex持续20分钟）。超过12周的眼部检查结果主要是结膜注射和眼排出。这些是短暂而温和的。组织病理学检查表明眼睛正常。>结论：采用Visulex系统可以安全有效地将DSP应用于兔眼。治疗时间和DSP浓度是达到治疗水平的重要因素。重复施用DSP-Visulex是安全的，并且可以耐受4-12周的每周一次给药。 DSP-Visulex在眼科疾病的无创治疗方面具有临床潜力。
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