左氧氟沙星滴眼液的兔眼内药代动力学研究

目的研究0.3%左氧氟沙星局部应用给兔眼后,在泪液和房水中的药动学行为.方法采用新西兰大白兔,双侧眼准确滴入0.3%左氧氟沙星滴眼液后,分别于不同时间取出房水和滤纸片并对其定量(定容及称重).组织中的药物浓度采用反相高效液相色谱荧光检测法定量测定.药动学参数采用非线性最小二乘法进行计算机拟合求得.结果采用反相高效液相色谱荧光检测法可以将左氧氟沙星同其他杂质很好分离,最低定量浓度为0.005μg/ml,测定不同时间组织中药物浓度结果表明左氧氟沙星滴眼后,5min时泪液左氧氟沙星浓度最高(1108.86μg/g±712.08μg/g;),30min时房水浓度最高(1.21μg/ml±0.43μg/ml).测得泪液中的药物浓度半衰期为27.05min,房水中为54.65min.结论左氧氟沙星能在眼内达到较高的抗菌浓度,可治疗眼内常见感染性疾病.     

加替沙星和左氧氟沙星治疗细菌性结膜炎的疗效对比研究

目的 探讨氟喹诺酮类抗生素加替沙星和左氧氟沙星治疗细菌性结膜炎的临床疗效和安全性.方法 采用多中心、随机、双盲、对照试验.2006年8月至2007年10月,在复旦大学附属眼耳鼻喉科医院、河南省眼科研究所、温州医学院附属视光医院、南京医科大学第一附属医院、第四军医大学西京医院、西安交通大学医学院第二附属医院6所医院进行研究.以盐酸左氧氟沙星滴眼液为有效对照,将诊断为细菌性结膜炎的235例(235只眼)患者按随机区组法分入两组:试验组118只眼,对照组117只眼,试验组滴用加替沙星,对照组滴用左氧氟沙星,每组给药方法均为每次2滴,第1-2天,每2小时滴1次,8次/d;以后每4小时滴1次,4次/d,滴入结膜囊内,疗程为7 d.所有人组患者均在试验开始前及试验结束后行结膜囊细菌培养及药物敏感试验,并在用药前和用药后第3-5天、第6-8天分别对症状、体征观察进行综合评分以及评价其安全性.采用协方差分析方法、CMH X2方法、Pearson X2检验、Fisher检验对实验数据进行统计学分析.结果 加替沙星组和左氧氟沙星组的有效率分别为94.0%(110/117只眼)和93.8%(106/113只眼),差异无统计学意义(X2=0.052,P=0.8201).加替沙星组和左氧氟沙星组的细菌清除率分别为94.1%(80/85只眼)和92.5%(74/80只眼),两组比较差异无统计学意义(P=0.3470).用药后第3～5天症状体征综合评分下降幅度加替沙星组为(4.436±2.310)分,左氧氟沙星组为(3.814±1.962)分,差异有统计学意义(F=7.280,P=0.0075).用药后第6～8天症状体征综合评分下降幅度加替沙星组为(7.487 ±2.821)分,左氧氟沙星组为(6.912±2.911)分,差异有统计学意义(F=4.060,P=0.0452).视力及局部用药后耐受性评分在两组之间无显著差异(视力F=1.04,P=0.3080;局部用药后耐受性X2=0.1372,P=0.7111).根据全部患者细菌培养结果,细菌性结膜炎致病菌以革兰阳性菌为主(共检测出革兰阳性菌20种,革兰阴性菌8种),加替沙星对革兰阳性菌的最低抑菌浓度低于左氧氟沙星(表皮葡萄球菌、金黄色葡萄球菌、凝固酶阴性葡萄球菌、甲型溶血性链球菌等).结论 加替沙星滴眼液对细菌性结膜炎有良好的治疗作用,能够有效清除致病菌,起效快,作用强,且体外抗菌活性高,不易产生耐药性,具备良好的安全性和眼部耐受性.     

左氧氟沙星白芨多糖滴眼液的眼部药物代谢动力学研究

目的评价5g.L-1左氧氟沙星白芨多糖滴眼液(左氧白芨滴眼液)滴兔眼后,药物在眼部的药物代谢动力学,以及与5g.L-1左氧氟沙星滴眼液(可乐必妥)比较其相对生物利用度。方法新西兰大白兔64只(128眼),平均分为2组,实验组给予左氧白芨滴眼液50μL滴眼,对照组给予可乐必妥50μL滴眼。分别于不同时间点取房水和角膜,应用高效液相色谱法测定左氧氟沙星浓度。采用DASver2.0药物代谢动力学程序计算各药物代谢动力学参数。结果所建立的高效液相色谱法能将左氧氟沙星与其他杂质很好地分离,其最低定量浓度为53.95μg.L-1,组织中回收率稳定。左氧白芨滴眼液与可乐必妥在房水中的半衰期(t1/2)分别为90.512min和106.480min,达峰时间(tmax)分别为45.000min和60.000min,达峰浓度(Cmax)分别为2318.973μg.L-1和1111.457μg.L-1(P<0.05);角膜中t1/2分别为109.400min和64.956min,tmax分别为10.000min和15.000min,Cmax分别为23.012μg.g-1和16.389μg.g-1。左氧白芨滴眼液组房水和角膜中药物...     

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。     

左氧氟沙星透明质酸钠滴眼液眼部药代动力学与生物利用度研究

目的研究0.3%左氧氟沙星透明质酸钠滴眼液滴眼后的药代动力学行为以及与同质量浓度普通处方比较相对生物利用度。方法采用新西兰大白兔,实验组双侧眼分别准确滴入0.3%的左氧氟沙星透明质酸钠滴眼液50μl,对照组双侧眼分别准确滴入0.3%盐酸左氧氟沙星滴眼液50μl,分别于不同时间取泪液、角膜与房水对其定量,药物质量浓度采用反相高效液相色谱法(HPLC)测定。药代动力学参数采用3p87药代动力学软件计算拟合求得。结果反相HPLC法可以将左氧氟沙星同其他杂质很好分离,最低定量质量浓度为0.05μg/m l,在组织中平均回收率为76.35%。测定0.3%的左氧氟沙星透明质酸钠滴眼液与对照组给药后泪液药物半衰期分别为8.27、7.81 m in,角膜消除相半衰期为146.38、128.31 m in,房水消除半衰期为59.78、51.82 m in。房水达峰质量浓度分别为1.621、0.995μg/m l。药物的泪液、角膜和房水质量浓度-时间曲线下面积AUC0-240分别是对照组的1.8、1.6和1.9倍。结论0.3%左氧氟沙星透明质酸钠滴眼液同对照组比较,其相对生物利用度显著提高。     

高效液相色谱法评估左氧氟沙星的眼内通透性

目的：评估左氧氟沙星滴眼液入眼通透性。采用高效液相色谱法(HPLC)测定33例白内障手术患者房水中左氧氟沙星滴眼液的浓度。

方法：共33例接受超声乳化术的患者，术前、术后3d均使用左氧氟沙星点眼，每6h滴1滴，术前1h停止给药。采用HPLC和荧光检测器测定左氧氟沙星在房水中的浓度。

结果：采用HPLC测定房水中左氧氟沙星含量，验证了该方法简便、有效、灵敏。左氧氟沙星浓度在1.95×10^-3-1.50 μg/mL的范围内呈线性关系，在房水中平均含量为0.3399±0.03405 μg/mL。

结论：本研究结果显示，白内障术前常规剂量(每6h滴1滴)0.5%左氧氟沙星不会引发急性细菌性眼内炎。     

人眼滴用氧氟沙星和环丙沙星及妥布霉素的前房穿透性研究

目的 比较人眼滴用氧氟沙星、环丙沙星及妥布霉素的前房穿透性差异。方法 2003年4～8月在我院门诊预行白内障超声乳化术的老年白内障患者125例(125只单侧眼),使用随机数字表分为3个大组：氧氟沙星组(42只眼),环丙沙星组(41只眼),妥布霉素组(42只眼),每个大组再使用随机排列表分为5个小组,每个小组8或9只眼。按不同大组,术前局部给予0．3％氧氟沙星、0．3％环丙沙星或0．3％妥布霉素,滴眼6次,每次间隔15min。手术时按不同小组,于最后1次给药后7．5、15．0、30．0、60．0、120．0min时抽取前房水约100μl。使用高效液相色谱仪分析前房水中药物浓度。结果 各时间点前房内氧氟沙星浓度均明显高于环丙沙星,氧氟沙星生物利用度是环丙沙星的6倍。高效液相色谱仪未能检测到妥布霉素,故其浓度低于最低检测限0．05μg／ml。结论 人眼滴用氧氟沙星、环丙沙星和妥布霉素的结果表明氧氟沙星前房穿透性最好,提示可作为预防和治疗眼内炎的首选局部用药。     

左氧氟沙星滴眼液在白内障术后人眼房水中质量浓度的定量研究

目的 定量分析白内障患者术前不同时间、不同频次应用左氧氟沙星滴眼液后房水中药物的质量浓度.方法 随机选取白内障患者90例(90眼),均实行白内障超声乳化摘出联合人工晶状体植入术,分为A、B、c组,A组为术前1 d点眼,每日4次;B组为术前1 d点眼,每日6次;C组为术前3 d连续点眼.每日4次.所有患者均在术前1.5 h进行最后1次点眼,术中取房水0.1 mL,即保存于-20℃的冰箱中.采用高效液相色谱法检测房水中的药物质量浓度,并进行组间比较.结果 房水中药物质量浓度A组为(0.68±0.58)μg/mL,B组为(1.05±0.66)μg/mL,C组为(1.89±0.98)μg/mL,B组高于A组,C组高于B组及A组,差异均有统计学意义(P<0.05).结论 房水中左氧氟沙星药物质量浓度与点药时间及频次呈正相关,为临床围手术期用药提供了良好的实验依据.     

薄壁滤过泡对左氧氟沙星滴眼液进入兔眼晶状体的影响

目的研究兔眼薄壁滤过泡形成后局部滴用左氧氟沙星滴跟液晶状体内浓度的变化。设计实验研究。研究对象新西兰白兔。方法将右眼行联合丝裂霉素C的巩膜咬切术后形成苍白、隆起、薄壁滤过泡的新西兰白兔26只,随机分为A、B、C三组。其中A、B组各8只,每日4次双眼滴左氧氟沙星滴眼液,每次0．1ml,分别持续4天和7天;C组10只,每30分钟双眼滴左氧氟沙星滴眼液一次,共点8次。i组全部最后一次滴左氧氟沙星滴眼液半小时后处死兔,取出晶状体,通过高效液相法（HPLC）检测晶状体中左氧氟沙星的浓度,分别比较各组中薄壁滤过泡眼与自身健康对照眼晶状体左氧氟沙星浓度的差别,比较各组之间薄壁滤过泡眼品状体左氧氟沙星浓度的差别。主要指标兔眼晶状体中左氧氟沙星浓度。结果三组中薄壁滤过泡眼（A组：0．33±0．10μg／g;B组：0．27±0．15μg／g;C组：0．62±0．28μg／g）与自身健康对照眼（A组：0．12±0．03μg／g;B组：0．12±0．03μg/g;C组：O．15±0．05μg／g）晶状体中左氧氟沙星浓度差异有统计学意义（A组：P〈0．0001;B组：P〈0．05;C组：P〈0．0001）,A组和B组薄壁滤过泡跟晶状体左氧氟沙星浓度差异无统计学意义（P=0．566）,A、B组与C组薄壁滤过泡眼晶状体左氧氟沙星浓度差异有统计学意义（P=0．006;0．001）,C组（0．62±0．28μg坛）薄壁滤过泡眼晶状体中左氧氟沙星浓度分别高于A组（0．33±0．10μg／g）和B组（0．27±0．15μg／g）。薄壁滤过泡结膜下大片疏松区域,结膜上皮萎缩变薄,结膜基底层细胞不规则,间隙增宽,炎症细胞浸润。结论薄壁滤过泡形成后,眼内晶状体中左氧氟沙星浓度增高,频繁点药品状体内左氧氟沙星浓度增高更为明显。     

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。     

Corneal penetration of fluoroquinolones: aqueous humor concentrations after topical application of levofloxacin 0.5% and ofloxacin 0.3% eyedrops

PURPOSE: To investigate the penetration of topically applied levofloxacin 0.5% and ofloxacin 0.3% eyedrops into the aqueous humor of patients having cataract surgery. SETTING: Hochkreuzklinik Eye Hospital, Bonn, Germany. METHODS: In this randomized, investigator-masked study, 69 patients received 4 drops of either levofloxacin 0.5% or ofloxacin 0.3% eyedrops within 1 hour (60 min, 45 min, 30 min, and 15 min) of elective cataract surgery. Aqueous humor samples of at least 50 muL were drawn from the anterior chamber at the beginning of the cataract operation. The concentrations of the fluoroquinolones in the anterior chambers were measured using high-performance liquid chromatography. To exclude a dilution effect of the anterior chamber (AC), they were related to the AC volumes (measured by 3-dimensional modeling of central Orbscan [Bausch & Lomb] slit-image photos) and AC depths (measured by ultrasound). RESULTS: The mean concentration of levofloxacin (1139.9 ng/mL +/- 717.1 [SD]) in the aqueous humor was significantly higher (P = .0008) than that of ofloxacin (621.7 +/- 368.7 ng/mL). The aqueous humor concentrations correlated negatively with the measured volumes and depths of the ACs. CONCLUSIONS: The new fluoroquinolone, levofloxacin, is more soluble in water enabling the use of higher drug concentrations (0.5%) compared with other currently available fluoroquinolone eyedrops (0.3%). The concentration AC with levofloxacin eyedrops was about 2-fold that reached with ofloxacin eyedrops. The concentration of the antibacterial isomer was approximately 3.5 to 4 times higher when levofloxacin was administered, assuming negligible stereoselective uptake.     

Penetration of topically applied levofloxacin 0.5% and ofloxacin 0.3% into the vitreous of the non-inflamed human eye

Background The aim of the study was to evaluate the vitreous penetration of two commercially available ophthalmic fluoroquinolones: ofloxacin and levofloxacin.Methods This prospective, double-blind, randomized clinical trial comprised 16 patients scheduled for vitrectomy surgery of one eye for macular hole or macular pucker. The patients were randomly assigned to receive topical ofloxacin 0.3% (n=9) or levofloxacin 0.5% (n=7) the day before, one drop at noon, 4 p.m., 8 p.m. and midnight. The next morning, patients were given their assigned masked antibiotic every 5 min for four doses starting 1 h before surgery. The vitreous humour samples, at least 0.3 ml each, were collected 1 h after the administration of the last dose, at the beginning of the pars plana vitrectomy with infusion disconnected. Samples were assayed for ofloxacin and levofloxacin concentrations by a method using high-performance liquid chromatography (HPLC) coupled with single mass spectrometry with electrospray ionization (ESI-MS).Results Equal topical administration of levofloxacin yielded 2.5 times higher vitreal concentration than ofloxacin. The mean vitreous concentrations of ofloxacin and levofloxacin were 5.30±3.04 (SD) ng/ml and 13.09±5.24 ng/ml, respectively (P=0.002).Conclusion Equal dosing with topical administration of levofloxacin 0.5% and ofloxacin 0.3% allows better penetration into the vitreous for levofloxacin, but the levels of mean concentrations of each drug did not exceed the MIC(90) or MIC(50) for most ocular pathogenic bacteria in terms of conventional endophthalmitis therapy.This study was supported financially in part by Santen Oy, Tampere, Finland.     

Ocular penetration and pharmacokinetics of topical gatifloxacin 0.3% and moxifloxacin 0.5% ophthalmic solutions after keratoplasty

PURPOSE: To compare the corneal and aqueous penetration and pharmacokinetics of gatifloxacin 0.3% and moxifloxacin 0.5% ophthalmic solutions and their effect on corneal reepithelialization after penetrating keratoplasty. METHODS: In this randomized, open-label, parallel-controlled study, corneal and aqueous penetration and the pharmacokinetic parameters of topically applied gatifloxacin 0.3% and moxifloxacin 0.5% (2 preoperative doses of 1 drop given 5 minutes apart) were estimated by using a sparse sampling method. Corneal and aqueous samples were collected 0.25, 0.5, 1, or 2 hours after the final dose. The concentration was determined by a high-performance liquid chromatography method. Stromal Cmax:MBC50 (maximum drug concentration in serum to 50% minimum bactericidal concentration) ratios for selected ocular pathogens were also assessed. Postoperative corneal reepithelialization at days 1, 3, and 7 was evaluated and compared between groups. RESULTS: The calculated pharmacokinetic parameters were higher with moxifloxacin 0.5% than with gatifloxacin 0.3%. The stromal Cmax was 48.5 versus 15.7 microg/g (P = 0.04), and the stromal AUC0-2 (area under the concentration-time curve from 0 to 2 hours) was 30.9 versus 13.6 mug.h/g (P < 0.05). The endothelial Cmax was 76.1 versus 7.3 microg/g (P > 0.05), and the endothelial AUC0-2 was 43.9 versus 9.8 microg.h/g (P < 0.05). The aqueous Cmax was 0.9 versus 0.3 microg/mL (P > 0.05), and the aqueous AUC0-2 was 1.2 versus 0.4 microg.h/mL (P < 0.05). Stromal Cmax:MBC50 ratios were higher in the moxifloxacin 0.5% group for each pathogen tested. The corneal reepithelialization rates were comparable between groups. CONCLUSIONS: Topical preoperative moxifloxacin 0.5% achieved greater corneal and aqueous penetration than did gatifloxacin 0.3%. The clinical significance of this difference is not known. Postoperative use of these agents had similar effects on corneal reepithelialization.     

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.     

Aqueous humor levels of topically applied levofloxacin, norfloxacin, and lomefloxacin in the same human eyes

PURPOSE: To assess the relative penetration of topical eyedrops of 3 fluoroquinolones into the aqueous humor in human eyes. SETTING: Department of Ophthalmology, Sano-Kosei Hospital, Sano, Japan. METHODS: Fifty-nine cataract patients (36 women, 23 men) received 3 drops each of levofloxacin 0.5%, norfloxacin 0.3%, and lomefloxacin 0.3% in the same eye at 15-minute intervals beginning 90 minutes before cataract surgery. At the beginning of surgery, 50 microL of aqueous humor was aspirated from the anterior chamber and stored at -80 degrees C until analyzed. The drug concentrations in the samples were analyzed using high-performance liquid chromatography. RESULTS: Five patients were excluded from the study because their sample volumes were insufficient. Norfloxacin was detected in 3 patients; the mean aqueous humor level was 0.10 microg/mL +/- 0.02 (SD). Levofloxacin was detected in all cases; the mean aqueous humor level was 0.60 +/- 0.28 microg/mL (n = 54). Lomefloxacin was not detected in 10 patients; the mean aqueous humor level was 0.23 +/- 0.11 microg/mL (n = 44). CONCLUSION: Topically applied levofloxacin had better penetration into the aqueous humor than lomefloxacin and norfloxacin.     

Effect of gatifloxacin 0.3% and moxifloxacin 0.5% ophthalmic solutions on human corneal epithelium following 2 dosing regimens

PURPOSE: To determine whether gatifloxacin 0.3% ophthalmic solution or moxifloxacin 0.5% ophthalmic solutions are toxic to the corneal epithelium when used with 1 of 2 dosing regimens in healthy human eyes. SETTING: Price Vision Group, Indianapolis, Indiana, USA. METHODS: In this double-masked randomized fellow-eye comparison study, gatifloxacin 0.3% was instilled in 1 eye and moxifloxacin 0.5% in the other eye either 4 times a day for 7 days or hourly for 10 hours. Before and after dosing, all eyes were examined with a slitlamp and the cell layers in the central cornea were evaluated by confocal microscopy. Subject discomfort with study drop instillation was also assessed. RESULTS: There was no statistically significant increase in the incidence or severity of superficial punctuate keratitis following use of gatifloxacin 0.3% or moxifloxacin 0.5% when instilled 4 times a day for 7 days or hourly for 10 hours. Hourly use of gatifloxacin 0.3% for 10 hours resulted in a mild but statistically significant increase in conjunctival hyperemia (P = .029). Use of moxifloxacin 0.5% resulted in a small but statistically significant deterioration of the corneal epithelial surface as assessed by confocal microscopy (P = .045). The incidence of subject discomfort with study drop instillation was comparable for the 2 antibiotics (P = .67). CONCLUSION: Use of ophthalmic solutions of gatifloxacin 0.3% or moxifloxacin 0.5% did not result in clinically significant epithelial toxicity in healthy human corneas after dosing regimens of 4 times a day for 7 days or hourly for 10 hours dosing regimens.     

Effect of gatifloxacin ophthalmic solution 0.3% on human corneal endothelial cell density and aqueous humor gatifloxacin concentration

PURPOSE: To evaluate the effect of gatifloxacin ophthalmic solution 0.3% (Zymar, Allergan, Inc., Irvine, CA, USA) on corneal endothelial cell density and morphology and to measure gatifloxacin penetration into aqueous humor. METHODS: This was a single-center, open-label clinical study. Ten patients undergoing standard cataract surgery and 20 nonsurgical subjects instilled gatifloxacin 0.3% four times per day for 2 days, then every 10 min for 1 hr on the third day (the surgery day for the cataract patients). Corneal endothelial cells were counted using noncontact specular microscopy. Anterior chamber fluid was withdrawn from the surgical patients, and the gatifloxacin concentration was quantified by high-pressure liquid chromatography. RESULTS: Baseline endothelial cell counts (mean +/- SD) were 2400 +/- 442 in the surgical group and 2520 +/- 212 in the nonsurgical group. The mean differences from baseline 1 hr after the last dose of gatifloxacin 0.3% were -51 +/- 213 (p = 0.23) in the surgical group and -7 +/- 150 (p = 0.42) in the nonsurgical group. In the nonsurgical group, the mean difference from baseline 3 weeks after the last dose was 18 +/- 147 (p = 0.71). The mean concentration (+/- SD) of gatifloxacin in aqueous humor was 1.26 +/- 0.55 microg/ml. CONCLUSIONS: A preoperative, prophylactic course of gatifloxacin 0.3% ophthalmic solution did not significantly affect endothelial cell density or morphology, while meaningful drug concentration was achieved in the aqueous humor.     

Aqueous humor levels of topically applied levofloxacin in human eyes

PURPOSE: To evaluate transcorneal penetration of topically applied 0.5% levofloxacin into the aqueous humor in human eyes. METHODS: Twenty cataract patients (14 females, 6 males) received 3 drops of 0.5% levofloxacin at 15 min intervals from 90 minutes before the surgery. At the beginning of the cataract surgery, 50 microL of aqueous humor was aspirated from the anterior chamber and stored at -80 degrees C until analysis. The drug concentration of the samples was analyzed using high-performance liquid chromatography. RESULTS: A mean aqueous humor level of levofloxacin was 1.00 +/- 0.48 microg/mL (mean +/- standard deviation, n = 20), ranging from 0.30 microg/mL to 2.32 microg/mL. CONCLUSIONS: The mean concentration of levofloxacin in the aqueous humor was higher than the MIC(90) values against some common pathogens of postoperative endophthalmitis, although a great degree of interpatient variability was present.     

The successful treatment of gatifloxacin-resistant Staphylococcus aureus keratitis with Zymar (gatifloxacin 0.3%) in a NZW rabbit model

PURPOSE: To determine whether gatifloxacin-resistant S. aureus (Gat-R-Sa) keratitis could be successfully treated with topical Zymar (gatifloxacin 0.3%) in a rabbit model. DESIGN: Experimental animal study. METHODS: Two separate studies were performed each using two clinical isolates of Gat-R-Sa, with MICs of 12 and 64 mug/ml to gatifloxacin. Study 1 consisted of four treatment groups (Zymar, Quixin [levofloxacin 0.5%], Ciloxan [ciprofloxacin 0.3%], and saline).Study 2 consisted of Zymar, cefazolin 50 mg/ml, vancomycin 50 mg/ml, and saline. Rabbits were infected intrastromally with 2,000 cfu in both eyes. Topical therapy began after four hours, every 15 minutes for 5 hours. After therapy, the eyes were graded for clinical signs of infection (blepharitis, conjunctivitis, iritis, corneal edema, and corneal infiltrates), and the corneas were homogenized to determine viable bacterial counts. RESULTS: Study 1: for both isolates, Zymar-treated eyes demonstrated significantly lower clinical scores compared with Ciloxan and saline, and significantly decreased the number of viable bacteria recovered compared with all groups. Study 2: for both isolates, Zymar and cefazolin demonstrated significantly lower clinical scores compared with vancomycin and saline. Zymar, cefazolin, and vancomycin significantly decreased the number of viable bacteria recovered compared with the saline control. CONCLUSIONS: We demonstrated the "Proof of Principle" that in vitro antibiotic resistance, based on CLSI standards, does not always correlate with in vivo treatment failure in the eye. An aggressive treatment regimen with Zymar appears to overcome in vitro resistance, resulting in the successful treatment of Gat-R-Sa infections in the NZW rabbit keratitis model.