The Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland.
The Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Ophthalmology. 2013 Mar;120(3):583-587. doi: 10.1016/j.ophtha.2012.09.014. Epub 2012 Dec 4.
To compare aqueous levels of fluocinolone acetonide (FAc) after administration of FAc inserts or FAc implants (Retisert; Bausch & Lomb, Rochester, NY).
Comparison of pharmacokinetics from 2 prospective, interventional, clinical trials.
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).
Aqueous FAc was measured after administration of FAc implants or 0.2 μg/day (low dose, ILUVIEN; Alimera Sciences Inc., Alpharetta, GA) or 0.5 μg/day (high dose) FAc inserts.
The primary end point was aqueous levels of FAc.
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 >6 ng/ml through 15 months, the last time point with measurements from at least 6 eyes.
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.
比较氟轻松醋酸酯（FAc）植入物或 FAc 植入剂（Retisert；Bausch & Lomb，罗彻斯特，NY）给药后房水中的水平。
两项前瞻性、干预性临床试验的药代动力学比较。
37 例糖尿病性黄斑水肿（DME）患者（Fluocinolone Acetonide in Human Aqueous [FAMOUS] 研究，C-01-06-002）和 7 例葡萄膜炎患者（NA-00019318）。
在给予 FAc 植入物或 0.2 μg/天（低剂量，ILUVIEN；Alimera Sciences Inc.，Alpharetta，GA）或 0.5 μg/天（高剂量）FAc 插入物后测量房水中的 FAc。
主要终点是房水中的 FAc 水平。
在接受 1 种治疗的受试者给药后 1 个月，FAc 插入物的平均房水 FAc 水平分别为 2.17（低剂量）和 3.03ng/ml（高剂量），FAc 植入物的平均房水 FAc 水平为 6.12ng/ml，最大水平分别为 3.83、6.66 和 13.50ng/ml。3 个月时，FAc 水平分别为 1.76、2.15 和 6.12ng/ml。低剂量插入物后 6 至 36 个月，FAc 的房水水平非常稳定，范围为 1.18 至 0.45ng/ml。高剂量插入物后，6 至 24 个月时 FAc 水平稳定，范围为 1.50 至 0.84ng/ml，然后在 30 个月时降至 0.35ng/ml，在 36 个月时降至 0.15ng/ml。在含有植入物的眼中，FAc 水平通过 15 个月保持 >6ng/ml，这是最后一次至少有 6 只眼进行测量的时间点。
低剂量和高剂量 FAc 插入物均提供了 FAc 的稳定长期释放，在房水中具有可比的峰值水平：约 3 个月内略有 >2ng/ml，然后稳定在 1.0 至 0.5ng/ml 之间，持续 36 个月低剂量插入物，而高剂量插入物则在 24 个月内保持 1.5 至 1.1ng/ml 之间的水平。FAc 植入物后的房水稳态水平 >6ng/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眼压升高存在剂量效应。在易感患者中，房水中 FAc 水平持续 >1ng/ml 会中度增加青光眼的风险，而水平 >6ng/ml 则会显著增加风险。
