兔眼局部应用氧氟沙星和妥布霉素的房水移行性实验研究

目的比较氧氟沙星和妥布霉素在兔眼局部使用的房水移行性。方法取28只家兔随机分成2组。分别于滴眼后10、20、30、40、60、90、120分钟后抽取房水。右眼点氧氟沙星,左眼点妥布霉素。另取7只兔作为空白对照组。给予生理盐水滴眼。采用高效液相法检测房水内的药物浓度。结果滴眼后兔前房内的药物浓度高峰值出现时间,氧氟沙星在滴眼后30～40min,妥布霉素在滴眼后20min左右。参照各自的MIC90值,氧氟沙星在给药后20min时房水浓度达到MIC90,可持续到60min。结论氧氟沙星具有良好的房水移行性,房水内药物浓度高。持续时间长。     

老年性白内障术中前房注射不同剂量曲安奈德预防炎症反应的研究

目的探讨老年性白内障术中前房注射不同浓度曲安奈德（TA）控制术后炎症反应的效果。方法老年性白内障手术60例（60眼）,随机分为3组,每组20眼。A组在手术结束时向前房内注射TA0．1mg／0．2mL;B组前房内注射rrA0．2mg／0．2mL。A、B组术后滴妥布霉素滴眼液,4次／d,连用1周。C组（对照组）,手术结束时前房内注射灌注液,术后滴妥布霉素地塞米松滴眼液,4次／d,连用3周。术后随访1个月。术后6～8h测量眼压,术后1d、2d、7d、15d、30d观察前房细胞及房水闪光,测量眼压、检查视力及眼底。结果术后1d、2d、7d、15d、30d,3个组之间前房细胞比较（P=1）,房水闪光比较（P=1）,差异均无统计学意义,术后6～8h,1d、2d、7d、15d、30d,3个组之间眼压比较,差异无统计学意义。结论老年性白内障术中前房注射0．1mg／0．2mL或0．2mg／0．2mL的曲安奈德都能有效地控制术后的炎症反应,无明显不良影响,重要的是术后可以不用糖皮质激素,从而减少了频繁滴眼的麻烦,也避免了由其引起的并发症。     

术前常用滴眼液对角膜内皮及角膜厚度的影响

目的 讨论白内障手术前常规使用的左氧氟沙星滴眼液、妥布霉素滴眼液及普拉洛芬滴眼液滴眼对角膜内皮细胞密度及角膜厚度的影响.方法 白内障手术前120例(120眼),随机分为6个组.术前分别以4次/d及1次/h两种频率滴用左氧氟沙星滴眼液、妥布霉素滴眼液及普拉洛芬滴眼液连续3d,检测用药前后角膜内皮细胞密度及角膜厚度.结果 3种滴眼液按照两种使用频率连用3d,用药前后角膜内皮细胞密度及中央角膜厚度自身对照比较差异均无统计学意义(t=- 1.595～1.608,P＞O.05).结论 左氧氟沙星、妥布霉素及普拉洛芬滴眼液对角膜内皮细胞密度及角膜厚度的并无明显影响.     

妥布霉素玻璃酸钠滴眼液在超声乳化白内障摘出术后的应用

目的评价妥布霉素玻璃酸钠滴眼液在超声乳化白内障摘出术后应用的临床有效性和安全性。方法随机、双盲筛选出白内障患者121例（121眼）施行超声乳化白内障摘出联合人工晶状体植入术，分为试验组和对照组，试验组术后滴用妥布霉素玻璃酸钠滴眼液，对照组术后滴用妥布霉素地塞米松滴眼液，分别于术后第1d、用药后第3、7、14d观察眼部症状和体征，并进行统计学分析。结果两组术后泪膜破裂时间、结膜充血、睫状充血、房水闪辉等比较，差异有统计学意义（P〈0．05）；角膜内皮细胞计数、视力、眼压等比较差异无统计学意义（P〉0．05）。结论对部分手术创伤小，反应轻的超声乳化白内障摘出术后的患者可以使用妥布霉素玻璃酸钠滴眼液。     

强化妥布霉素滴眼液治疗绿脓杆菌性角膜溃疡的临床观察

目的 探讨1．34％强化妥布霉素滴眼液治疗绿脓杆菌性角膜溃疡的方法和疗效。方法 26例（26眼）随机分成两组．每组13例（13眼）。强化浓度组（A组）：1.34％妥布霉素滴眼液滴眼；对照组（B组）0．3％妥布霉素滴眼液滴眼。两组均接受全身加局部同种和相同剂量的抗生素及激素治疗。分别观察两组角膜溃疡局限、前房积脓吸收、角膜水肿消退平均时间、病原菌培养结果和治愈后1个月最佳矫正视力，统计学处理采用t检验。结果 两组病例角膜溃疡均得到控制，所有病例均得以保留眼球，视力得到不同程度改善。强化治疗组角膜溃疡局限、前房积脓吸收时间短于对照组，经统计学分析差异有显著性。两组病原菌培养结果和治愈后1个月最佳矫正视力分布差异经统计学分析差异无显著性。结论 妥布霉素滴眼液为治疗绿脓杆菌性角膜溃疡的一线药物，强化妥布霉素频繁点眼可以快速达到较高组织浓度，加快角膜溃疡愈合过程，是有效而且安全的治疗方法。     

强化妥布霉素滴眼液在外因性细菌性眼内炎治疗中的应用

目的：探讨强化妥布霉素滴眼液治疗急性外因性细菌性眼内炎的方法和疗效.方法：54例随机分成两组,每组27例（27眼）.强化治疗组（A组）：13.4g/L妥布霉素滴眼液滴眼;对照组（B组）3g/L妥布霉素滴眼液滴眼.两组均进行前房冲洗加前房注射万古霉素,辅以全身加局部同种和相同剂量的抗生素及激素治疗.分别观察两组房水渗出全部吸收平均时间、角膜水肿完全消退平均时间、房水病原菌培养结果和术后1mo最佳矫正视力,统计学处理采用t检验.结果：两组病例眼内炎症均得到控制,大部分视力得到不同程度改善.强化治疗组房水纤维素性渗出吸收时间短于对照组,统计学分析有显著性差异.两组房水病原菌培养结果和术后1mo最佳矫正视力分布差异没有统计学意义.结论：对于急性外因性细菌性眼内炎,在及时前房冲洗、前房注药治疗或者联合玻璃体切割术之外,13.4g/L强化妥布霉素滴眼液频繁滴眼有利于眼内炎症控制,是有效而且安全的辅助治疗方法.     

白内障超声乳化术后当天开放滴眼的临床观察

目的　观察白内障超声乳化术后早期开放滴眼对患者的影响。方法　随机抽取老年性白内障患者1997例 (2 0 0只眼 ) ,分为两组 ,滴眼组术后立即在结膜囊滴复方地塞米松妥布霉素滴眼液 ,消毒带孔塑料眼罩包眼。术后当天开放滴眼 ,每 2小时 1次 ,2小时、4小时及 2 4小时后接受检查。对照组术后结膜囊内涂复方妥布霉素眼膏 ,包绵质眼垫 ,2 4小时后接受检查。记录手术中超声乳化能量复合参数 (平均超声乳化能量×平均超声乳化时间 )、术后视力、角膜水肿、前房反应、患者感受、眼睑肿胀及结膜水肿 ,进行比较分析。结果　两组术中超声乳化能量复合参数比较差异无显著性 ;术后视力、角膜水肿、前房反应、异物感比较差异也无显著性 ;眼睑肿胀、结膜水肿两组比较差异有显著性。结论　白内障超声乳化术后早期开放滴眼更有利于患者尽早康复     

三种抗炎药物在Nd：YAG激光后囊膜切开术后应用的随机对照研究

背景Nd：YAG激光后囊膜切开术是治疗后发性白内障的重要手段,通常术后常规使用糖皮质激素滴眼液点眼以减轻患者术眼的前房炎症反应,但这存在升高眼压的潜在风险。目的比较氯替泼诺混悬滴眼液、妥布霉素地塞米松滴眼液和氟米龙滴眼液在Nd：YAG激光后囊膜切开术后局部应用的抗炎效果及对眼压的影响。方法采用随机对照研究设计,对接受Nd：YAG激光后囊膜切开术的127例患者171眼按随机数字表法随机分为4个组：氯替泼诺组35例47眼,采用氯替泼诺混悬滴眼液点眼;氟米龙组30例40眼,使用氟米龙滴眼液点眼;妥布霉素地塞米松组29例38眼,给予妥布霉素地塞米松滴眼液点眼;聚乙二醇组33例46眼,使用聚乙二醇滴眼液点眼。4个组均于Nd：YAG激光后囊膜切开术后开始点眼,每日6次,连续使用5d。分别于术前1h及术后1h、1d、3d、1周使用Glodmann眼压计测量眼压,在裂隙灯显微镜下按照Peizeng的标准对术眼的前房炎症反应程度进行评分。结果氯替泼诺组术眼术前1h,术后1h、1d、3d及1周的平均眼压分别为（18．2±4．7）、（20．1±5．7）、（18．7±5．5）、（19．0±4．1）和（19．5±3．5）mmHg;氟米龙组分别为（18．7±5．3）、（20．9±5．7）、（21．3±4．5）、（21．0±4．9）、（22．5±6．5）mmHg;妥布霉素地塞米松组分别为（17．9±6．3）、（20．3±6．1）、（23．0±3．7）、（24．7±4．9）、（24．5±6．5）mmHg;聚乙二醇组分别为（18．4±6．3）、（20．7±3．7）、（22．7±6．5）、（19．6±4．8）、（18．5±3．5）mmHg,4个组术眼眼压的总体比较差异有统计学意义（F组别3．876,P：0．023）;随着时间的延长,氯替泼诺组和聚乙二醇组眼压逐渐下降,而氟米龙组和妥布霉素地塞米松组眼压均高于术前,总体比较差异有统计学意义（F时间=3．801,P=0．031）。各组均未见其他明显眼部和全身药物相关性不良反应。氯替泼诺组和妥布霉素地塞米松组用药后房水细胞分级为1级和2级的百分比明显低于氟米龙组和聚乙二醇组,差异有统计学意义（H=8．276,P=0．012）;氯替泼诺组术眼I级房水闪辉的百分比为8％,氟米龙组为22％,妥布霉素地塞米松组为18％,聚乙二醇组为30％,各组房水闪辉严重程度的总体比较差异有统计学意义（H=9．305,P=0．000）。结论Nd：YAG激光后囊膜切开术后局部使用糖皮质激素能有效减轻患者术眼的前房炎症反应,其中氯替泼诺滴眼液抗炎疗效更好,对眼压影响较小,不良反应少,可作为Nd：YAG激光后囊膜切开术后的常规局部用药。     

羊膜对氧氟沙星滴眼液兔角膜通透性的影响

目的探讨羊膜对氧氟沙星滴眼液兔角膜通透性的影响。方法先给108只新西兰大白兔进行样本编号,再按号码单纯随机抽样并分为6组,每组18只,分别为正常角膜组、正常角膜羊膜移植组、机械刮除角膜上皮组、机械刮除上皮联合羊膜移植组、角膜碱烧伤组、角膜碱烧伤联合羊膜移植组。0．3％氧氟沙星眼液滴眼,每15min滴眼1次,共4次,最后1次滴眼后5、30min,1、2、4、6h,于每个时间点每组18只大白兔中任意处死3只兔抽取房水。高效液相法检测房水中氧氟沙星的浓度。结果刮除角膜上皮组与正常角膜上皮组比较,药物的前房浓度均明显增高（均P〈0．05）。正常角膜羊膜移植组5、30min、1h房水中氧氟沙星浓度与正常角膜组无明显差异（均P〉0．05）,而2、4、6h则明显高于正常角膜组（均P〈0．05）;机械刮除上皮联合羊膜移植组2、4、6h房水中氧氟沙星浓度亦明显高于机械刮除角膜上皮组（均P〈0．05）,而两组间5、30min、1h房水中氧氟沙星浓度比较无明显差异（均P〉0．05）;角膜碱烧伤联合羊膜移植组6h以内房水中氧氟沙星浓度均高于碱烧伤组（均P〈0．05）。结论羊膜具有一定药物蓄积和缓释作用,增加了氧氟沙星在角膜表面的停留时间,使药物的通透性增高。     

0.5%左氧氟沙星与0.3%加替沙星及0.3%乳酸左氧氟沙星的房水药物浓度研究

目的 探讨人眼分别滴用0.5%左氧氟沙星、0.3%加替沙星及0.3%乳酸左氧氟沙星后房水中药物浓度差异.方法 采用随机、双盲、平行研究方法.选取2006年8月至2007年2月在浙江大学医学院附属第二医院眼科中心预行白内障超声乳化术的老年白内障患者150例(150只单侧眼),使用随机数字表法分为3个大组:0.5%左氧氟沙星组(50只眼)、0.3%加替沙星组(50只眼)、0.3%乳酸左氧氟沙星组(50只眼),每个大组冉使用随机排列表分为5个亚组,每个亚组10只眼.按不同大组,术前分别局部给予0.5%左氧氟沙星、0.3%加替沙星或0.3%乳酸左氧氟沙星滴眼,总共4次,每次间隔15 min.手术时按不同亚组,分别于最后1次给药后15、30、60、120、180 min时抽取房水多于100 μl,然后用加样器准确定量至100μl置于带塞试管中.全部标本采用高效液相色谱法测定房水中药物浓度.采用单因素方差分析(ANOVA)对不同时间点的3种药物浓度进行统计学分析,两两之间差异比较采用t检验进行分析.结果 给药后15、30、60、120、180 min房水内0.5%左氧氟沙星浓度(1.61±0.48)、(2.41±0.80)、(2.93±0.50)、(2.56±0.63)、(1.87±0.88)mg/L分别高于对应时间点的0.3%加替沙星浓度(0.70±0.18)、(1.29±0.54)、(1.59±0.67)、(1.41±0.50)、(1.13±0.28)mg/L及0.3%乳酸左氧氟沙星浓度(0.55±0.39)、(1.15±0.42)、(1.38±0.49)、(1.02±0.33)、(0.55±0.31)m.g/L,差异均有统计学意义(F=23.64,12.82,21.13,25.00,12.22;P均<0.05).0.3%加替沙星和0.3%乳酸左氧氟沙星的房水药物浓度经检验在15、30、60、120 min无明显差异(t=1.09,0.68,0.83,2.00;均P>0.05).在180 min时0.3%加替沙星的房水药物浓度高于0.3%乳酸左氧氟沙星,差异有统计学意义(t=4.36,P<0.05).结论 人眼滴用0.5%左氧氟沙星、0.3%加替沙星及0.3%乳酸左氧氟沙星后,以滴用0.5%左氧氟沙星后房水的药物浓度最高.     

Penetration of topically applied ciprofloxacin and ofloxacin into the aqueous humor and vitreous

PURPOSE: To determine the intraocular penetration of topical drops of 2 antibiotics, ciprofloxacin 0.3% and ofloxacin 0.3%, into the aqueous humor and vitreous and to relate these levels to the miminum inhibitory concentration (MIC(90)) for organisms associated with ocular bacterial infections. SETTING: Department of Ophthalmology, Ankara Hospital, and Department of Pharmacology, Faculty of Medicine, Hacettepe University, Ankara, Turkey. METHODS: This prospective randomized clinical trial comprised 18 patients having cataract surgery, all with an intact corneal epithelium. The patients were randomly assigned to receive topical ciprofloxacin 0.3% (n = 10) or topical ofloxacin 0.3% (n = 8) 1 drop every 15 minutes 5 times and every 30 minutes 3 times before surgery. Aqueous and vitreous samples (if vitreous loss occurred during the cataract surgery) were collected 30 minutes after the administration of the last dose. Drug concentrations were determined by high-performance liquid chromatography (HPLC) fluorescence. RESULTS: All patients had detectable drug concentrations in the aqueous humor and vitreous measurable by HPLC. The mean aqueous humor concentration of ciprofloxacin was 1.13 microg/mL +/- 1.90 (SD) and the mean vitreous concentration, 0.23 +/- 0.06 microg/mL. Topical administration of ciprofloxacin yielded 4.9 times more drug concentration in the anterior chamber than in the vitreous. The mean aqueous concentration of ofloxacin was 2.06 +/- 1.06 microg/mL and the mean vitreous concentration, 0.46 +/- 0.10 microg/mL. Topical administration of ofloxacin yielded 4.7 times more drug concentration in the anterior chamber than in the vitreous. Aqueous humor concentrations of ofloxacin and ciprofloxacin were not statistically significantly different (P =.353). Intravitreal concentrations of ofloxacin were statistically significantly higher than those of ciprofloxacin (P =.001). CONCLUSIONS: Topical ofloxacin 0.3% penetrated better than topical ciprofloxacin 0.3% into the anterior chamber and vitreous in noninflamed eyes. Both drugs were above the MIC(90) for most ocular pathogens in the anterior chamber. The mean concentration in the vitreous of topically applied ofloxacin 0.3% was statistically significantly higher than that of ciprofloxacin 0.3%, but it was not sufficiently above the MIC(90) for most ocular pathogens in terms of empirical endopthalmitis therapy.     

Penetration of ofloxacin and ciprofloxacin in aqueous humor after topical administration.

BACKGROUND AND OBJECTIVE: To compare the aqueous humor levels of 0.3% ofloxacin and 0.3% ciprofloxacin containing eyedrops in patients with healthy cornea. PATIENTS AND METHODS: Fifty patients with cataract were randomly assigned to have 0.3% ofloxacin containing eyedrop (25 patients) or 0.3% ciprofloxacin containing eyedrop (25 patients). Both drugs were repetitively instilled to each patient for 6 hours before the surgery. Aqueous samples were collected after penetrating the anterior chamber during cataract extraction and assayed by high-performance liquid chromatography method. RESULTS: The aqueous humor level of ofloxacin (1.43 +/- 0.26 microg/ml, mean +/- SEM) was significantly higher than that of ciprofloxacin (0.35 +/- 0.07 microg/ml) following the topical application (P < .0002). CONCLUSION: Aqueous humor penetration of topical ofloxacin is about 4 times higher than that of topical ciprofloxacin when the drugs are applied as described above.     

Penetration of second-, third-, and fourth-generation topical fluoroquinolone into aqueous and vitreous humour in a rabbit endophthalmitis model

AIMS: This study was designed to investigate the penetration of second-, third- and fourth-generation topical fluoroquinolone into aqueous and vitreous humour in a rabbit endophthalmitis model. METHODS: Thirty New Zealand white rabbits were divided into six groups. Left eye was infected with an intravitreal inoculum of Staphylococcus aureus. Groups 1, 2, 3, 4, and 5 received topical ofloxacin, ciprofloxacin, lomefloxacin, levofloxacin, or moxifloxacin treatment 24 h after the inoculation, respectively. No treatment was given to group 6 as the control group (n=5). Aqueous and vitreous samples were obtained 30 min after the last drop. High-performance liquid chromatography was used to determine the fluoroquinolone concentration. RESULTS: In the normal and inflamed eyes, mean aqueous concentrations of ofloxacin were 1.90 and 2.69 mug/ml, ciprofloxacin were 2.16 and 3.65 mug/ml, lomefloxacin were 3.54 and 1.19 mug/ml, levofloxacin were 2.89 and 9.41 mug/ml, and moxifloxacin were 4.92 and 43.33 mug/ml, respectively. Mean vitreous concentrations of ofloxacin were 0.25 and 0.07 mug/ml, ciprofloxacin were 0.08 and 0.32 mug/ml, lomefloxacin were 0.001 and 0.03 mug/ml, levofloxacin were 0.03 and 0.09 mug/ml, and moxifloxacin were 0.28 and 2.68 mug/ml, in normal and inflamed eyes, respectively. Moxifloxacin achieved a significantly higher concentration in aqueous and vitreous humour of infected eyes compared with ofloxacin (P<0.01), ciprofloxacin (P<0.05), lomefloxacin (P<0.01), and levofloxacin (P<0.05). CONCLUSION: This study demonstrated that fourth-generation fluoroquinolone, moxifloxacin, seems to have better penetration to inflamed ocular tissues in rabbit.     

The effect of long-term use and inflammation on the ocular penetration of topical ofloxacin.

PURPOSE. To study the penetration of ofloxacin into the aqueous and vitreous humors after long-term topical administration and to investigate the effects of inflammation on drug penetration in rabbits. METHODS. A standardized model of intraocular infection after penetrating injury was achieved in the right eyes of 16 rabbits. The animals were randomly and equally divided into two groups. The intact left eyes of the groups were maintained as the control. Ofloxacin eyedrops (0.3%) were instilled into all eyes at a frequency of 2 drops every hour for 7 hours in the first group and for 14 hours in the second group. Half an hour after the last drop, samples of the aqueous and vitreous humors were taken and ofloxacin concentrations were measured by using HPLC. RESULTS. The mean aqueous humor concentrations of ofloxacin in control eyes after 7 and 14 hours of instillation were: 1.45 +/- 0.93 microg/ml and 2.48 +/- 0.33 microg/ml, respectively; those in infected eyes 2.35 +/- 1. 84 microg/ml and 3.49 +/- 1.47 microg/ml, respectively. However the differences among the groups were not significant (p > 0.05). The vitreous ofloxacin concentrations in the control eyes were similar after 7 and 14 hours of instillation (0.23 +/- 0.14 microg/ml, 0.27 +/- 0.10 microg/ml, respectively). In infected eyes, the mean vitreous ofloxacin concentration after 14 hour of instillation was significantly higher than that in control eyes (p < 0.05; 0.4 +/- 0. 09 microg/ml, 0.29 +/- 0.11 microg/ml, respectively). The mean vitreous ofloxacin concentration in infected eyes after 14 hours instillation was not significantly higher than that after 7 hours instillation. CONCLUSIONS. Topical ofloxacin instillation for 7 or 14 hours yields aqueous concentrations above the MIC(90) for common ocular pathogens. Prolonged application and the presence of inflammation increased the penetration of ofloxacin into the vitreous humor.     

Concentrations of levofloxacin, ofloxacin, and ciprofloxacin in human corneal stromal tissue and aqueous humor after topical administration

OBJECTIVE: To evaluate the penetration of commercially available levofloxacin 0.5%, ofloxacin 0.3%, and ciprofloxacin 0.3% topical ophthalmic solutions in human corneal stromal and aqueous humor tissues. METHODS: A total of 67 patients scheduled to undergo penetrating keratoplasty for treatment of stromal scar or dystrophy, keratoconus, pellucid marginal degeneration, or endothelial disease were enrolled in this prospective, double-blind, 3-center study. To be considered for inclusion, patients had to have an intact corneal epithelium and minimal or no corneal edema (pachymetry < 650 microm). After informed consent was obtained, patients were randomized to receive 1 drop of levofloxacin 0.5%, ofloxacin 0.3%, or ciprofloxacin 0.3% topical ophthalmic solution at approximately 15 and 10 minutes before surgery. Approximately 0.1 mL of aqueous fluid was aspirated by paracentesis through the trephination wound at the onset of surgery, followed by excision of the affected cornea and removal of its epithelium. Specimens were stored frozen at -70 degrees C until assayed by high-performance liquid chromatography. RESULTS: All 3 fluoroquinolones were well tolerated. A total of 65 corneas and 59 aqueous fluid samples were obtained and assayed. The mean +/- standard deviation corneal concentrations of ciprofloxacin, ofloxacin, and levofloxacin following a 2-drop administration were 9.92 +/- 10.99 microg/g (n = 18), 10.77 +/- 5.90 microg/g (n = 23), and 18.23 +/- 20.51 microg/g (n = 24), respectively. Although corneal stromal levels were highest in the levofloxacin group, the high degree of interpatient variability prevented demonstration of statistically significant differences when compared with ofloxacin (P = 0.377). In contrast, levofloxacin concentrations were approximately twice as high as ciprofloxacin, and this difference reached statistical significance (P = 0.014). The corresponding aqueous humor concentrations of ciprofloxacin, ofloxacin, and levofloxacin were 0.135 +/- 0.231 microg/mL (n = 15), 0.135 +/- 0.111 microg/mL (n = 20), and 0.372 +/- 0.546 microg/mL (n = 24, P < 0.001 versus ciprofloxacin and ofloxacin). CONCLUSION: The topical administration of all 3 agents was well tolerated in patients undergoing penetrating keratoplasty. Two drops of levofloxacin 0.5% solution results in a 1.7- to 2.7-fold greater penetration into human corneal stromal and aqueous humor tissues than ofloxacin 0.3% or ciprofloxacin 0.3%. The mean intracorneal concentrations of all three agents following 2 drops exceeds the MIC90 for the majority of pathogens causing bacterial keratitis. Topical levofloxacin appears to offer pharmacokinetic and pharmacodynamic advantages over ofloxacin and ciprofloxacin in terms of enhanced transcorneal penetration; however, clinical comparative trials are needed to confirm these relative advantages.     

Penetration of topical and oral ciprofloxacin into the aqueous and vitreous humor in inflamed eyes.

PURPOSE: To assess the aqueous and vitreous penetration of ciprofloxacin after topical and combined topical and oral administration and investigate the effects of inflammation on drug penetration. METHODS: A standardized penetrating injury was made in the right eyes of 16 rabbits. Intraocular inflammation was induced by intravitreal injection of a suspension of Staphylococcus aureus in these eyes. The animals were divided into two groups according to treatment methodology: topical and topical-oral. The intact left eyes of the animals were maintained as controls. In the topical treatment group, two drops of ciprofloxacin 0.3% were instilled to both eyes every 30 minutes for 4 hours. In the topical-oral treatment group, animals were given two oral 40 mg/kg doses of ciprofloxacin at 12-hour intervals. After the last oral dose, the protocol of the topical group was applied to these eyes. Half an hour after the last drop, 100-microL samples were taken from aqueous and vitreous humor of all eyes. Drug concentrations were measured using high-pressure liquid chromatography. RESULTS: Mean aqueous levels of ciprofloxacin in control eyes were 2.31 microg/mL (range, 1.02-6.27 microg/mL) in the topical group and 5.88 microg/mL (1.52-17.81) in the topical-oral group. Mean aqueous levels in inflamed eyes were 7.36 microg/mL (2.34-17.15) in the topical group and 14.43 microg/mL (2.18-18.66) in the topical-oral group. Mean vitreous levels in control eyes were 0.77 microg/mL (0.09-1.93) in the topical group and 1.01 microg/mL (0.49-1.57) in the topical-oral group. Mean vitreous levels in inflamed eyes were 0.95 microg/mL (0.18-1.27) in the topical group and 1.98 microg/mL (0.51-3.34) in the topical-oral group. There was no significant difference among the groups (P > 0.05). Mean aqueous levels in all eyes and mean vitreous levels in the combined topical and oral group of inflamed eyes were above the 90% minimum inhibitory concentration for most of the common microorganisms causing endophthalmitis. CONCLUSION: There is an increase in both aqueous and vitreous humor concentrations with inflammation and with oral and topical administrations, as opposed to topical only, of ciprofloxacin. Using oral as well as topical treatment may be a beneficial method of antibiotic prophylaxis in ocular trauma once a patient has received intravenous or intravitreal therapy.     

Amniotic membrane, tear film, corneal, and aqueous levels of ofloxacin in rabbit eyes after amniotic membrane transplantation

PURPOSE: We evaluated ocular penetration and drug levels in tears after topical ofloxacin instillation in rabbit eyes with amniotic membrane transplantation (AMT). METHODS: Forty-eight New Zealand White rabbits were used. In the first set of experiments, 24 rabbits (24 eyes) were divided into four groups according to the epithelial removal or AMT. Topical ofloxacin was instilled four times every 15 minutes. One hour after the last eyedrop, the concentration of ofloxacin in the amniotic membrane, cornea, and aqueous humor was evaluated. In the second set of experiments, 24 rabbits were divided into six groups according to AMT (transplantation of lyophilized or fresh amniotic membrane) or duration of application. Ofloxacin ointment or two drops of ofloxacin were applied to the right eye, and then tear samples were collected after 0.5, 1, 2, 4, and 6 hours for the analysis of ofloxacin concentration. RESULTS: Mean ofloxacin concentrations in the cornea and aqueous humor were statistically higher in deepithelialized cornea regardless of AMT (p < 0.05). The mean tear levels of ofloxacin in the AMT groups were statistically higher than those in non-AMT groups (p < 0.05). There was no statistical significance in the tear level of ofloxacin between lyophilized amniotic membrane groups and fresh amniotic membrane groups nor between 1-hour amniotic membrane-attached groups and 6-hour amniotic membrane-attached groups. CONCLUSION: Amniotic membrane transplantation seems to interfere with the ocular penetration of topical ofloxacin in normal rabbit corneas but enhances ofloxacin penetration in corneas with epithelial defects. The ofloxacin level in tears was higher in eyes with AMT up to 1 hour after topical ofloxacin use. Therefore, it seems that amniotic membrane has some potential to act as an effective drug delivery system.     

Corneal and scleral permeability of quinolones--a pharmacokinetics study.

PURPOSE: To investigate the corneal and scleral permeability of nalidixic acid and synthesized fluoroquinolones and their in vivo pharmacokinetics in rabbits. METHODS: The corneal and scleral permeability coefficients of ciprofloxacin, norfloxacin, cinoxacin, enoxacin, and ofloxacin were determined in rabbits using high performance liquid chromatography (HPLC). The aqueous humor levels of norfloxacin and ciprofloxacin were measured separately by topical instillation of 0.3% solutions of the two drugs onto rabbit eyes. RESULTS: Nalidixic acid had a higher corneal permeability coefficient (17.3 +/- 3.56 x 10(-6) cm/second) than all other drugs tested (p < 0.01). Corneal permeability coefficients in rabbits among ciprofloxacin, norfloxacin, cinoxacin, enoxacin, and ofloxacin were not significantly different (p > 0.1). Comparing the corneal and scleral permeability coefficients, only values for nalidixic acid were not significantly different (17.35 +/- 3.56 x l0(-6) cm/second versus 22.69 +/- 5.19 x 10(-6) cm/second, p > 0.05), while all other drugs had scleral permeability coefficients 8 to 10 times greater than corneal permeability coefficients. The mean aqueous humor concentration of norfloxacin and ciprofloxacin at 60 minutes to 180 minutes after instillation was around 0.3 microg/mL, a value higher than MIC90 of most bacteria.     

Use of collagen corneal shields versus soft contact lenses to enhance penetration of topical tobramycin

We compared the corneal penetration in rabbits of topical tobramycin in the presence of collagen corneal shields and bandage soft contact lenses. A collagen corneal shield was placed on six albino rabbit eyes, while therapeutic soft contact lenses (61.4% poly-2-hydroxyethyl-methacrylate/38.6% water) were placed on six eyes. Four control eyes received no shield or contact lens. Topical tobramycin was applied to all 16 eyes every five minutes for six doses. Samples of aqueous humor were removed at 15 and 60 minutes following the last dose. Collagen corneal shields allowed a significant (P less than .05) increase in tobramycin penetration into the anterior chamber at 60 minutes compared with hydrophilic soft contact lenses or controls.