Blazaki S, Tsika C, Tzatzarakis M, Naoumidi E, Tsatsakis A, Tsatsanis C, Tsilimbaris Miltiadis K
Laboratory of Optics and Vision, Department of Ophthalmology, University of Crete, 71003, Heraklion, Crete, Greece.
Laboratory of Toxicology, Medical School, University of Crete, Heraklion, Greece.
Graefes Arch Clin Exp Ophthalmol. 2017 Dec;255(12):2375-2380. doi: 10.1007/s00417-017-3812-9. Epub 2017 Sep 29.
Intravitreal delivery of non-steroidal anti-inflammatory drugs could be an effective way to treat macular edema caused by posterior segment inflammation. In this study, we evaluated the intravitreal bioavailability and anti-inflammatory efficacy of flurbiprofen in rabbit eyes.
For pharmacokinetics, 0.1 ml of 7.66 mg/ml flurbiprofen solution was injected intravitreally and vitreous drug levels were analyzed at specific time points using LC-MS technique. For efficacy, 100 ng lipopolysaccharide of E.coli was injected intravitreally in rabbits to induce inflammation. The animals were separated in three groups and received intraocular flurbiprofen, dexamethasone and PBS to serve as control. Complete ocular examination and total cell count in aqueous fluid were determined to evaluate the extent of inflammation. Eyes were then enucleated for histopathology analysis. The efficacy in the uveitis model was determined by clinical signs of inflammation, total leukocyte count and histology findings.
No adverse events were observed during pharmacokinetic assessment. No signs of inflammation, hemorrhage or retina detachment were detected. The recovery of flurbiprofen from vitreous samples was 92.6%. The half-life of flurbiprofen was estimated to be 1.92 h with an elimination constant rate (K) of 0.36. Treatment with intraocular injections of flurbiprofen and dexamethasone significantly reduced total leukocyte count in a manner comparable to dexamethasone [reduction of 96.84% (p < 0.05) and 97.44% (p < 0.05), respectively]. Histologic studies demonstrated significantly less signs of ocular inflammation after flurbiprofen injection compared to control eyes.
Flurbiprofen is effective in suppressing inflammation in this experimental uveitis model. In our experimental setting, intravitreal flurbiprofen seem to have a therapeutic result comparable to dexamethasone. However, the half-life of the drug remains short, necessitating further research to prolong its presence in the vitreous cavity.
玻璃体内注射非甾体类抗炎药可能是治疗后段炎症引起的黄斑水肿的有效方法。在本研究中，我们评估了氟比洛芬在兔眼玻璃体内的生物利用度和抗炎效果。
在药代动力学研究中，将0.1 ml 7.66 mg/ml的氟比洛芬溶液玻璃体内注射，使用液相色谱-质谱技术在特定时间点分析玻璃体内药物水平。在药效学研究中，将100 ng大肠杆菌脂多糖玻璃体内注射到兔体内以诱导炎症。将动物分为三组，分别接受眼内注射氟比洛芬、地塞米松和磷酸盐缓冲液作为对照。进行完整的眼部检查并测定房水中的细胞总数以评估炎症程度。然后摘除眼球进行组织病理学分析。葡萄膜炎模型中的药效通过炎症的临床体征、白细胞总数和组织学结果来确定。
在药代动力学评估过程中未观察到不良事件。未检测到炎症、出血或视网膜脱离的迹象。氟比洛芬从玻璃体液样本中的回收率为92.6%。氟比洛芬的半衰期估计为1.92小时，消除常数率（K）为0.36。眼内注射氟比洛芬和地塞米松治疗均显著降低白细胞总数，与地塞米松相当[分别降低96.84%（p < 0.05）和97.44%（p < 0.05）]。组织学研究表明，与对照眼相比，注射氟比洛芬后眼部炎症迹象明显减少。
氟比洛芬在该实验性葡萄膜炎模型中可有效抑制炎症。在我们的实验环境中，玻璃体内注射氟比洛芬似乎具有与地塞米松相当的治疗效果。然而，该药物的半衰期仍然较短，需要进一步研究以延长其在玻璃体腔中的存在时间。
