Effect of loteprednol etabonate nasal spray suspension on seasonal allergic rhinitis assessed by allergen challenge in an environmental exposure unit

BACKGROUND: Loteprednol etabonate (LE) is a novel soft steroid that was designed to improve the benefit/risk ratio of topical corticosteroid therapy. This study assesses the clinical efficacy and safety of three different doses of LE nasal spray in seasonal allergic rhinitis (SAR). METHODS: In this single-center, double-blind, placebo-controlled, parallel-group trial 165 subjects with SAR to grass pollen received daily single doses of either 100, 200, 400 microg LE nasal spray, or placebo for 14 days. The patients underwent three 4-h allergen challenges with grass pollen in an environmental exposure unit at a screening visit (baseline) and on days 7 and 14 of treatment. Standardized nasal symptom scores were obtained every 20 min. Nasal flow, nasal secretions, and FEV(1) were measured every hour during allergen challenges. RESULTS: After 14 days of treatment, patients who received 400 microg LE had significantly lower total nasal symptom scores compared with those receiving placebo (P = 0.007). LE400 reduced rhinorrhea, nasal congestion, nasal itching, the amount of nasal secretions, and improved nasal flow as compared with placebo (P < 0.05). LE100 and LE200 were not significantly different from placebo. All treatments were well tolerated. CONCLUSIONS: Loteprednol 400 microg once daily is superior to placebo and the only effective dose tested in improving nasal symptoms and objective parameters in patients with SAR.     

Safety & efficacy of single subconjunctival triamcinolone 5 mg depot vs topical loteprednol post cataract surgery: less drop cataract surgery

AIM: To do a randomized prospective interventional study for comparing the effects of a single subconjunctival triamcinolone acetonide (SCTA) injection to tapering topical loteprednol in patients undergoing phacoemulsification surgery under topical anesthesia. METHODS: A total of 400 patients were randomized into 2 groups; Group A (200 patients) received 5 mg SCTA at the end of surgery and topical ketorolac tromethamine (0.5%) with ofloxacin (0.3%) combination for 3wk. Group B (200 patients) received tapering topical loteprednol etabonate (0.5%) along with ofloxacin (0.3%) and ketorolac tromethamine (0.5%) for 3wk. Outcomes evaluated were intraocular pressure (IOP), anterior chamber cells/flare and macular oedema postoperatively at 1, 6 and 12wk. RESULTS: Baseline parameters were almost similar in both the groups. No statistical difference was seen between the preoperative and postoperative IOP values for Group A (P=0.82) and Group B (P=0.61) and postoperative IOP values in between both groups (P=0.14) at 1wk. Incidence of cells/flare postoperative was statistically not significant (P=0.82) in both groups at all follow up visits. Postoperative macular oedema was not observed at any follow up visit. CONCLUSION: SCTA appears to be an effective alternative to prolong postoperative topical steroid use.     

Loteprednol etabonate for inflammatory conditions of the anterior segment of the eye: twenty years of clinical experience with a retrometabolically designed corticosteroid

Introduction: Topical corticosteroids are an important pharmacotherapy for the management of various inflammatory conditions affecting the anterior segment of the eye. However, medications in this class are associated with well-known risks including increased intraocular pressure (IOP) and development of cataracts. The topical corticosteroid loteprednol etabonate (LE) was developed with the specific intention of minimizing these side effects.

Areas covered: The focus of this review is to examine published efficacy and safety data for LE, a drug engineered to undergo rapid metabolism to inactive metabolites with the goal of improved safety. Two decades of clinical research focused on LE formulations are reviewed, including the use of LE in combination with tobramycin. The cumulative body of experience affirms the concept that the molecular design of LE confers certain safety benefits without compromising the desired anti-inflammatory efficacy of a topical corticosteroid.

Expert opinion: Loteprednol etabonate is a mainstay for topical therapy of a wide variety of commonplace and niche conditions of the ocular surface and the anterior segment, including in the healing post-operative patient. Its versatility and safety allow eye care providers to recommend both acute induction as well as chronic maintenance therapy with appropriate follow-up.     

Soft Drugs 18. Oral and Rectal Delivery of Loteprednol Etabonate,a Novel Soft Corticosteroid,in Rats—for Safer Treatment of Gastrointestinal Inflammation

Purpose. As a safe anti-inflammatory corticosteroid, the utility of loteprednol etabonate (LE) for the treatment of gastrointestinal inflammation, via oral and rectal administration, was investigated in rats. Methods. In vivo, LE solution and suspension were orally administered (20 mg/kg), and various LE preparations (solution, suspension & suppository) were applied in rectal loops (0.2 mg per loop). In vitro, various GI tissues were used to study the stability and partition of LE. Results. After oral administration of LE solution, LE reached the upper GI tract effectively, but not the colon, due to absorption and/or decomposition. In suspension, LE reached most of the GI tract (except rectum) in 8 hr and showed little absorption. After rectal applications, LE remained intact in the rectal loop for more than five hours with a slow rate of disappearance, however, LE distributed in the rectal membrane to some extent. The concentrations of LE and its inactive metabolites in plasma after both oral and rectal administrations were lower than the detection limit (0.1 µg/ml) at anytime during the experiments. In vitro, LE in solution was stable in stomach, but not in cecum, due to the hydrolysis by the cecal resident micro flora. In solution, LE distributed into the mucosal membranes efficiently (about 2.5 ~ 4.0 µg/g tissue). Conclusions. The results suggest that LE can be orally or rectally delivered in the GI tract for the topical treatment of the inflammatory bowel disease.     

环孢霉素A滴眼液治疗单疱病毒性角膜基质炎疗效观察

目的:观察10g/L环孢霉素A滴眼液治疗单疱病毒性角膜基质炎临床疗效。方法:我院2011-01/2012-01治疗单疱病毒性角膜基质炎患者91例91眼,随机分为两组,A组应用10g/L环孢霉素A滴眼液和更昔洛韦凝胶,B组应用5g/L氯替泼诺滴眼液和更昔洛韦凝胶,其余均为对症治疗,随诊观察6～12(平均10)mo。结果:两组治疗单疱病毒性角膜基质炎疗效无显著性差异,但A组治愈时间平均5.1±2.4d,B组治愈时间平均6.2±2.8d,A组较B组平均治愈时间短。两组治愈率及复发率无统计学差异。结论:对于单疱病毒性角膜基质炎患者应用10g/L环孢霉素A滴眼液能够安全有效治愈,且治愈时间短。     

氯替泼诺妥布霉素混悬滴眼液微生物限度检查方法的探讨

目的：建立氯替泼诺妥布霉素混悬滴眼液的微生物限度检查方法。方法：参照中国药典2005年版二部附录微生物限度检查方法进行试验。结果：采用直接接种法对人工污染的六种菌株进行试验,该药品对四株细菌有不同程度的抑菌作用．采用薄膜过滤法用0.1％蛋白胨水加聚山梨酯进行样品处理,300ml 0.1％蛋白胨水分三次冲洗,可消除其抑菌成分。结论：建立的氯替泼诺妥布霉素混悬滴眼液微生物限度检查方法简单,准确、可靠。     

HPLC梯度洗脱法测定氯替泼诺妥布霉素复方混悬滴眼液中氯替泼诺含量及有关物质

摘 要 目的： 建立HPLC梯度法测定氯替泼诺妥布霉素复方混悬滴眼液中氯替泼诺含量及有关物质。方法: 采用HPLC法,色谱柱：Inertsil ph苯基柱（250 mm×4.6 mm,5 μm）;流动相A：0.25%醋酸溶液 乙腈（80∶20）;流动相B：乙腈;流速：2.0 ml·min^-1,进行线性梯度洗脱;检测波长：244 nm;柱温：30℃;进样量：20 μl。结果: 主成分与各杂质峰分离度良好。氯替泼诺浓度在0.001~1.02 mg·mL^-1（r=0.999 9）范围内与峰面积线性关系良好,平均回收率为99.9%,RSD为0.9%（n=9）。结论:该方法灵敏准确,色谱峰分离完全,可用于氯替泼诺妥布霉素混悬滴眼液的质量控制。     

Comparison of Efficacy and Safety of Loteprednol Etabonate 0.5% and Topical Dexamethasone 1% in Post-Vitrectomy Inflammation

Purpose: To compare the efficacy and safety of postoperative topical loteprednol etabonate (LE) 0.5% with dexamethasone (DEX) 0.1% for the treatment of inflammation following pars plana vitrectomy (PPV).

Methods: A total of 150 eyes of 150 patients who underwent transconjunctival PPV for various diagnoses were included in this prospective, randomized study. The patients were assigned into two groups as Group LE (n = 75) and Group DEX (n = 75). Intraocular inflammation, intraocular pressure (IOP), and the intensity of postoperative pain were compared between the groups.

Results: The mean IOP was higher in the patients treated with DEX (p > 0.05). The need for anti-glaucoma medications was significantly lower in Group LE (5.3%) than in Group DEX (17.3%) (p = 0.020). Tyndall scores were less in Group DEX at postoperative Days 1 (p = 0.01) and 3 (p = 0.017). On Day 1, it was more likely for patients to have mild or moderate pain in Group LE (p < 0.001). On Day 3, the number of the patients with no pain was higher in Group DEX (p = 0.005).

Conclusions: Although DEX is more effective in the early postoperative days, LE appears to be as effective in controlling inflammatory response following PPV in the long-term. Topical LE is associated with less increase in the IOP and a lower need for anti-glaucoma medications.     

LASIK术后质量分数0.5％氯替泼诺滴眼液应用的随机对照研究

背景 近视性准分子激光角膜原位磨镶术(LASIK)后需局部使用糖皮质激素滴眼液已成为共识,具有良好抗炎效果且不良反应小的糖皮质激素滴眼液有利于术后角膜上皮的快速修复.目的 评估质量分数0.5％氯替泼诺滴眼液在LASIK术后的临床应用效果.方法 采用前瞻性随机对照研究设计.本研究经中山大学中山眼科中心伦理委员会批准,所有患者纳入前均充分了解本研究的内容并签署知情同意书.112例224眼纳入研究,其中共97例194眼完成随访.双眼接受近视性LASIK的患者以随机数字表法分为0.5％氯替泼诺滴眼液点眼组(试验组)54例108眼和对照组43例86眼,两组患者年龄及术前等效球镜度差异均无统计学意义(P＞0.05).两组的基础治疗方法一致.试验组从术后第1天开始局部点用0.5％氯替泼诺滴眼液,每日4次,共1周,对照组以同样的方法点用妥布霉素地塞米松滴眼液.分别于术后1d、1周、1个月对2个组患者的主观症状进行评分,并行裸眼视力、最佳矫正视力(BCVA)、眼压、中央角膜厚度、角膜荧光素染色检查,同时观查术眼的术中和术后并发症情况,以评价0.5％氯替泼诺滴眼液点眼的安全性.结果 在随访过程中,未观察到与药物相关的全身和眼部严重并发症.术后1d、1周和1个月,试验组和对照组主观症状评分(包括眼痛、异物感、视物模糊评分)比较,差异均无统计学意义(P＞0.05).术后1周,试验组和对照组校正后的实际眼压分别为(16.27±3.31)mmHg和(17.49±4.48)mmHg,差异有统计学意义(t=-2.113,P=0.036);术后1个月,试验组和对照组校正后的实际眼压分别为(15.01±3.22)mmHg和(15.30±4.17)mmHg,差异无统计学意义(t=-0.532,P=0.595).术后1d,试验组发生轻度弥漫性层间角膜炎(DLK)者7眼,对照组为5眼,差异无统计学意义(x2 =0.153,P=0.926),术后1周和1个月两组中均未发现DLK.术后1d、1周和1个月两组间的角膜荧光素染色评分差异均无统计学意义(Z=-0.566,P=0.571;Z=-0.689,P=0.491;Z=-1.628,P=0.103).结论 0.5％氯替泼诺滴眼液用于LASIK术后可以有效控制术后炎症反应和DLK,并且减少了传统糖皮质激素升高眼压的风险.     

Loteprednol Etabonate 0.5%/Tobramycin 0.3% Compared with Dexamethasone 0.1%/Tobramycin 0.3% for the Treatment of Blepharitis

Purpose: To compare the efficacy of loteprednol etabonate 0.5%/tobramycin 0.3% (LE/T) and dexamethasone 0.1%/tobramycin 0.3% (DM/T) ophthalmic suspensions in reducing select signs of blepharitis.

Methods: Data were pooled from two studies (one from the USA; one from China) of adults (n = 627) with blepharokeratoconjunctivitis treated with LE/T or DM/T four times daily for 2 weeks (safety population). Efficacy analyses included 495 eyes (247 LE/T, 248 DM/T) with any baseline sign of blepharitis.

Results: At Day 15, the least squares mean change from baseline in composite blepharitis severity was similar between LE/T (–2.86) and DM/T (–2.99) (90% CI for mean treatment difference: –0.35, 0.11). Intraocular pressure (IOP) increases ≥10 mmHg over baseline were reported for 1 US patient (DM/T group) and 19 Chinese patients (6 LE/T; 13 DM/T).

Conclusions: LE/T was similarly effective in reducing the signs of blepharitis compared with DM/T, but demonstrated a better safety profile with respect to changes in IOP.