Aqueous Levels of Fluocinolone Acetonide after Administration of Fluocinolone Acetonide Inserts or Fluocinolone Acetonide Implants
Aqueous Levels of Fluocinolone Acetonide after Administration of Fluocinolone Acetonide Inserts or Fluocinolone Acetonide Implants
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DOI：
10.1016/j.ophtha.2012.09.014
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发表时间：
2013-03-01
期刊：
影响因子：
13.7
通讯作者：
Kane, Frances E.
中科院分区：
文献类型：
--
作者：
Campochiaro, Peter A.;Quan Dong Nguyen;Kane, Frances E.
目的：比较给予 FAc 插入物或 FAc 植入物（Retisert；Bausch & Lomb，罗彻斯特，纽约）后房水中氟轻松丙酮 (FAc) 的水平。设计：比较 2 项前瞻性、介入性临床试验的药代动力学。参与者：37 名糖尿病性黄斑水肿 (DME) 患者（氟轻松丙酮在人房水 [FAMOUS] 研究中， C-01-06-002)和7名葡萄膜炎患者(NA-00019318)。方法：在施用FAc植入物或0.2μg/天低剂量ILUVIEN后测量水性FAc； Alimera Sciences Inc., Alpharetta, GA) 或 0.5 μg/天（高剂量）FAc 插入物。主要结果指标：主要终点是 FAc 的水溶液水平。结果：接受 1 次治疗的受试者给药后 1 个月，FAc 插入物的平均水性 FAc 水平为 2.17（低剂量）和 3.03 ng/ml（高剂量），FAc 为 6.12 ng/ml植入物的最高水平分别为 3.83、6.66 和 13.50 ng/ml。 3 个月时，平均 FAc 水平分别为 1.76、2.15 和 6.12 ng/ml。低剂量插入后 6 至 36 个月之间，FAc 水溶液水平非常稳定，范围为 1.18 至 0.45 ng/ml。高剂量插入后，平均 FAc 水平在 6 至 24 个月内保持稳定，范围为 1.50 至 0.84 ng/ml，然后在 30 个月时降至 0.35 ng/ml，在 36 个月时降至 0.15 ng/ml。在含有植入物的眼睛中，平均 FAc 水平在 15 个月内保持 > 6 ng/ml，最后一个时间点至少对 6 只眼睛进行测量。结论：低剂量和高剂量 FAc 插入物均提供稳定的长期 FAc 释放，并且在水中具有可比较的峰值水平：约 3 个月略大于 2 ng/ml，随后 36 个月内稳定在 1.0 至 0.5 ng/ml 之间的稳态水平，而低剂量插入物与 2 之间的水平相比对于高剂量插入物，24 个月内为 1.5 和 1.1 ng/ml。 FAc 植入后的稳态水浓度>6 ng/ml。这些结果提供了新的见解，有助于解释疗效试验，并表明类固醇引起的高眼压存在剂量效应。在易感患者中，长期房水中FAc水平>1 ng/ml会中度增加青光眼的风险，而水平>6 ng/ml则会显着增加风险。 财务披露：专有或商业披露可在参考文献后找到。眼科 2013；120:583-587 (C) 2013，美国眼科学会。
Purpose: To compare aqueous levels of fluocinolone acetonide (FAc) after administration of FAc inserts or FAc implants (Retisert; Bausch & Lomb, Rochester, NY).Design: Comparison of pharmacokinetics from 2 prospective, interventional, clinical trials.Participants: Thirty-seven patients with diabetic macular edema (DME) (Fluocinolone Acetonide in Human Aqueous [FAMOUS] Study, C-01-06-002)and 7 patients with uveitis (NA-00019318).Methods: Aqueous FAc was measured after administration of FAc implants or 0.2 mu g/day low dose, ILUVIEN; Alimera Sciences Inc., Alpharetta, GA) or 0.5 mu g/day (high dose) FAc inserts.Main Outcome Measures: The primary end point was aqueous levels of FAc.Results: At 1 month after administration for subjects who received 1 treatment, mean aqueous FAc levels were 2.17 (low dose) and 3.03 ng/ml (high dose) for FAc inserts and 6.12 ng/ml for FAc implants with maximum levels of 3.83, 6.66, and 13.50 ng/ml, respectively. At 3 months, mean FAc levels were 1.76, 2.15, and 6.12 ng/ml, respectively. Between 6 and 36 months after low-dose inserts, aqueous levels of FAc were remarkably stable, ranging from 1.18 to 0.45 ng/ml. After high-dose inserts, mean FAc levels were stable between 6 and 24 months, ranging from 1.50 to 0.84 ng/ml and then decreasing to 0.35 ng/ml at 30 months and 0.15 ng/ml at 36 months. In implant-containing eyes, mean FAc levels remained >6ng/ml through 15 months, the last time point with measurements from at least 6 eyes.Conclusions: Low-and high-dose FAc inserts both provide stable long-term release of FAc with comparable peak levels in the aqueous: slightly >2 ng/ml for approximately 3 months followed by steady-state levels between 1.0 and 0.5 ng/ml through 36 months for low-dose inserts versus levels between 1.5 and 1.1 ng/ml through 24 months for high-dose inserts. Steady-state aqueous levels after FAc implants were >6 ng/ml. These results provide new insights that aid in the interpretation of efficacy trials and indicate that there is a dose effect for steroid-induced ocular hypertension. In susceptible patients, prolonged aqueous levels of FAc >1 ng/ml moderately increased the risk of glaucoma and levels >6 ng/ml posed a markedly increase risk.Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references. Ophthalmology 2013;120:583-587 (C) 2013 by the American Academy of Ophthalmology.