加替沙星原位凝胶的体外释放及兔眼房水药动学研究

目的:研究加替沙星温敏型凝胶及离子敏感型凝胶的体外释药特性、机制及在家兔房水中的药动学特征。方法:采用无膜溶出法考察凝胶的体外溶蚀及药物释放;局部滴入加替沙星凝胶剂或滴眼液,以HPLC法测定兔眼房水中的药物浓度,计算药动学参数。结果:凝胶溶蚀与药物释放速率均随着振荡频率和释放面积的增加而增大,两者具有明显的相关性;给药后8 h内,温敏、离子敏感凝胶组与滴眼液组房水中药物峰浓度分别为(1.38±0.11)μg·mL-1、(1.19±0.20)μg·mL-1及(0.50±0.06)μg·mL-1,达峰时间分别为2.0 h、1.0 h和1.0 h,AUC0-8h分别为(5.61±0.25)μg·h·mL-1、(4.50±0.19)μg·h·mL-1和(1.29±0.22)μg·h·mL-1。结论:凝胶溶蚀与药物释放行为符合零级动力学方程,药物的释放主要由凝胶溶蚀决定。加替沙星凝胶剂较滴眼液可显著提高房水中的药物浓度及生物利用度并延长了作用时间。     

加替沙星滴眼液在兔眼角膜中的药动学

目的 探讨加替沙星滴眼液单次滴兔眼后在角膜中的药动学特征.方法 24只新西兰家兔,局部滴入加替沙星滴眼液50μl,以高效液相色谱法测定兔眼角膜中加替沙星的药物浓度,用DAS1.0软件计算药动学参数.结果 给药后0.5～6 h,加替沙星在兔眼角膜中的最高浓度为(3.18±1.39)μg/g,消除半衰期(t1/2)为(2.33±0.58)h,药-时曲线下面积AUC0-6h为(7.40±2.07)μg/(h·g).空白角膜不干扰加替沙星的含量测定.结论 加替沙星滴眼液单次滴兔眼后在眼角膜中具有良好的药动学特征和组织通透性.     

利奈唑胺滴眼液在家兔房水中的浓度及其药代动力学特征

目的探讨利奈唑胺滴眼液单次滴兔眼后在房水中的浓度及其药代动力学特征。方法 54只新西兰家兔,局部滴入利奈唑胺滴眼液50 ml,采用高效液相色谱法测定兔眼房水中利奈唑胺的药物浓度,计算其药代动力学参数。结果给药后0～120 h,利奈唑胺在兔眼房水中的达峰浓度为(84.92±67.04)μg/ml,消除半衰期t1/2为(43.28±38.11)h,药时曲线下面积AUC0～t为(1 747.44±871.36)μg.h.ml-1,AUC0～∞为(2 335.25±1 102.42)μg.h.ml-1。空白房水不干扰利奈唑胺的含量测定。结论利奈唑胺滴眼液单次滴兔眼后在房水中具有良好的药动学特征和组织通透性。     

加替沙星滴眼液在兔眼房水中的药动学

目的探讨加替沙星滴眼液单次滴兔眼后在房水中的药动学特征。方法24只新西兰家兔,局部滴入加替沙星滴眼液50μL,以高效液相色谱法测定兔眼房水中加替沙星的药物浓度,用DAS1.0软件计算药动学参数。结果给药后0.5～6 h,加替沙星在兔眼房水中的c_(max)为(0.31±s 0.06)mg·L~(-1),消除半衰期为(3.4±0.7)h,AUC_(0～6h)为(0.70±0.22)mg·h·L~(-1),AUC_(0～∞)为(0.7±0.3)mg·h·L~(-1)。空白房水不干扰加替沙星的含量测定。结论加替沙星滴眼液单次滴兔眼后在眼房水中具有良好的药动学特征和组织通诱性。     

利奈唑胺滴眼液在家兔房水中的浓度及其药代动力学特征

目的 探讨利奈唑胺滴眼液单次滴兔眼后在房水中的浓度及其药代动力学特征.方法 54只新西兰家兔,局部滴人利奈唑胺滴眼液50ml,采用高效液相色谱法测定兔眼房水中利奈唑胺的药物浓度,计算其药代动力学参数.结果 给药后0～120h,利奈唑胺在兔眼房水中的达峰浓度为(84.92±67.04)μg/ml,消除半衰期t1/2为(4...     

0.5%莫西沙星滴眼液和0.3%加替沙星滴眼液预防眼科术后感染有效性的系统评价

目的:系统评价0.5%莫西沙星(MXFX)滴眼液和0.3%加替沙星(GTF)滴眼液预防眼科术后感染的有效性。方法:计算机检索PubMed、EMbase、西文生物医学期刊文献数据库和中国期刊全文数据库,收集以0.5%MXFX滴眼液和0.3%GTF滴眼液作为眼科清洁手术预防用药的随机对照试验(RCT),按照Cochrane系统评价方法对符合纳入标准的文献提取房水药物浓度和药物不良反应资料,对提取的房水药物浓度与眼内炎常见病原菌最小抑菌浓度(MIC)进行对比,采用Rev Man 4.2统计软件对有效数据进行Meta分析。结果:共纳入9篇文献14项RCT,合计747例患者。Meta分析结果显示,0.5%MXFX滴眼液和0.3%GTF滴眼液的房水药物浓度比较差异有统计学意义[SMD=1.26,95%CI(1.03,1.48),P<0.000]。0.5%MXFX的房水药物浓度可以达到眼内炎常见病原菌的MIC,而0.3%GTF只能达到凝固酶阴性葡萄球菌和金黄色葡萄球菌的MIC。结论:0.5%MXFX滴眼液可有效预防眼科术后感染,其房水药物浓度显著高于0.3%GTF滴眼液,能达到眼内炎常见致病菌的MIC。由于纳入文献的数量较少,质量较低,该结论还需大样本、多中心、高质量的RCT进一步证实。     

地塞米松磷酸钠在兔眼房水中的药动学研究

目的 探讨地塞米松磷酸钠滴眼液单次滴兔眼后在眼房水内的药动学特征.方法 采用18只新西兰家兔,局部滴入地塞米松磷酸钠滴眼液50μl,以高效液相色谱法测定眼房水中地塞米松磷酸钠的药物浓度,用DASl.0软件计算药动学参数.结果 给药后0.25～6 h,地塞米松磷酸钠在房水中的最高浓度(3.553±0.4287)μg/ml,消除半衰期t1/2,2为(1.44±0.56)h,药时曲线下面积AUC0-6 h为(10.41±2.87)μg·h·ml-1,AUC0-8为(11.47 4-3.64)μg·h·ml-1.空白房水不干扰地塞米松磷酸钠的含量测定.结论 地塞米松磷酸钠滴眼液单次滴兔眼后在眼房水中具有良好的药动学特征和组织通透性.     

老年性白内障手术围术期是否全身预防使用抗菌药物对比研究

目的:探讨老年白内障手术围术期仅局部应用抗菌药物滴眼液的可行性。方法:采用回顾性分析方法,将我院2011年1-6月与2012年1-6月进入老年白内障临床路径行白内障手术的患者,为A、B组,A组围术期给予抗菌药物滴眼液+全身预防性使用,B组围术期仅眼局部给予抗菌药物滴眼液,比较2组患者眼内炎发生率。结果:2组患者术后眼内炎发生率均为0。结论:进入老年性白内障临床路径的患者,在白内障手术围术期可以仅眼局部应用抗菌药物滴眼液,而不需全身预防性使用抗菌药物。     

三联手术对白内障并发急性闭角型青光眼患者术后血—房水屏障功能的影响

目的:观察超声乳化白内障吸除折叠式人工晶状体植入联合青光眼小梁切除术(三联手术)对血—房水屏障影响,评价三联手术安全性.方法:回顾性分析13例(13眼)年龄相关性性白内障并发急性闭角型青光眼患者,通过药物治疗眼压降至正常范围后行三联手术.结果:术前1d及术后7、30和90d房水闪辉值分别为19.808±3.456、41.153士8.418、14.844±5.107、13.942士6.875,术前1d与术后7、30和90d的房水闪辉值比较有显著性差异(P＜0.05),术前1d较术后7d房水闪辉值低,但较术后30及90d房水闪辉值高;术后7d较术后30、90d的房水闪辉值高(P＜0.05);术后30d与90d房水闪辉值比较无统计学差异(P＞0.05).术前1d、术后7、30和90d眼压分别为(52.270士6.960)mmHg、(13.935士4.361)mmHg、(14.385士3.230)mmHg、(15.089士2.597)mmHg,各时间点眼压与房水闪辉值之间无线性相关性(P＞0.05).结论:年龄相关性性白内障并发急性闭角型青光眼患者行三联手术后血—房水屏障破坏较为严重,术后积极抗炎治疗减轻手术损伤,是保证三连手术成功的关键.     

乳酸左氧氟沙星滴眼液在兔眼房水中的药代动力学

目的 :测定乳酸左氧氟沙星 (LVFX)滴眼液单次滴眼后不同时间兔眼房水的药物浓度 ,计算其药动学参数。方法 :取32只大白兔分为8组 ,各组于用药后0 125、0 25、0 50、0 75、1 0、2 0、3 0、4 0h取眼房水 ,用高效液相色谱法测定药物浓度。结果 :用3p87药动学程序拟合符合一室开放模型 ,药物在房水中Tmax0 940h、Cmax 0 592μg/ml、T1/2(Ka)0 479h、T1/2(Ke)0 919h。结论 :单次滴眼后兔房水中LVFX峰浓度均高于大多数致病菌的MIC90,LVFX滴眼液可用于眼内感染的临床治疗和预防。     

Comparative evaluation of aqueous and plasma concentration of topical moxifloxacin alone and with flurbiprofen in patients of cataract surgery

Objectives:

To determine the aqueous and plasma concentrations of moxifloxacin administered topically alone and with flurbiprofen in patients undergoing cataract surgery.

Materials and Methods:

A total of 50 subjects scheduled for routine cataract surgery were randomly allocated to two groups (n = 25 each). Group-1 patients were treated with topical moxifloxacin alone: One drop 6 times/day for 3 days before surgery and one drop 4 times on the day of surgery: Group-2 patients were treated with topical moxifloxacin as in Group-1 and with topical flurbiprofen: One drop 4 times/day for 3 days before and on the day of surgery. The interval between two drugs was 30 min for last 3 days and 15 min on the day of surgery. Last dose was administered 1 h before aqueous humor and blood sampling for both the groups. The antibiotic concentration in aqueous humor and plasma were determined by using high performance liquid chromatography.

Results:

The mean concentration of moxifloxacin in aqueous humor was 1.71 ± 0.82 mg/ml in Group-1 and 2.39 ± 1.34 mg/ml in Group-2. Concentrations of moxifloxacin in aqueous humor were significantly higher in Group-2 than that of Group-1.

Conclusion:

Flurbiprofen may increase the concentration of moxifloxacin in aqueous humor.KEY WORDS: Aqueous humor, cataract surgery, flurbiprofen, moxifloxacin     

Ocular penetration of moxifloxacin 0.5% and gatifloxacin 0.3% ophthalmic solutions into the aqueous humor following topical administration prior to routine cataract surgery

A prospective, double-masked, randomized, parallel-group study (n = 25) was conducted to examine the ocular penetration of moxifloxacin 0.5% ophthalmic solution and gatifloxacin 0.3% solution into the aqueous humor following topical administration prior to routine cataract surgery. One drop of antibiotic was instilled every 10 min for four doses beginning 1 h prior to surgery. Preliminary results showed aqueous humor concentrations for moxifloxacin that were significantly greater (p < 0.01) than those for gatifloxacin.     

Effect of nasolacrimal occlusion on timolol concentrations in the aqueous humor of the human eye.

We studied the effect of manual nasolacrimal occlusion on the concentration of timolol in the aqueous humor of eyes of patients undergoing cataract extraction. Aqueous humor samples were obtained at various times after timolol maleate instillation from patients with or without 5 min of nasolacrimal occlusion; aliquots were assayed by HPLC. In patients receiving occlusion treatment, average timolol concentrations were statistically greater than those in control patients both between 15 and 90 min after instillation and also at 180 min. Pharmacokinetic analysis indicated that occlusion increased the concentration of timolol in the aqueous humor 1.7 times. In both groups, timolol concentrations were highest approximately 1 h after instillation. The decline in aqueous humor timolol concentrations occurred at similar rates in both groups.     

Ocular penetration of moxifloxacin 0.5% and gatifloxacin 0.3% ophthalmic solutions into the aqueous humor following topical administration prior to routine cataract surgery

ABSTRACT

A prospective, double-masked, randomized, parallel-group study (n = 25) was conducted to examine the ocular penetration of moxifloxacin 0.5% ophthalmic solution and gatifloxacin 0.3% solution into the aqueous humor following topical administration prior to routine cataract surgery. One drop of antibiotic was instilled every 10?min for four doses beginning 1?h prior to surgery. Preliminary results showed aqueous humor concentrations for moxifloxacin that were significantly greater (?p < 0.01) than those for gatifloxacin.     

盐酸利多卡因眼用凝胶在兔眼房水中药物浓度测定及药动学研究

目的：建立兔眼房水中利多卡因的LC-MS/MS检测方法,研究盐酸利多卡因眼用凝胶在兔眼房水中的药动学特征。方法：72只雄性新西兰兔分成Ⅰ和Ⅱ两组,每组36只,Ⅰ和Ⅱ组分别给予盐酸利多卡因眼用凝胶受试制剂和参比制剂,左右眼均滴入15μL,于不同时间点取房水样品,经沉淀蛋白后,采用LC-MS/MS法测定房水中的利多卡因。以来曲唑为内标,采用Hanbon Hedera ODS-2 C18（2.1 mm×150 mm,5μm）色谱柱,流动相为甲醇-20 mmol·L-1醋酸铵水溶液（含0.1%甲酸）（55∶45,v/v）,质谱采用气动辅助电喷雾离子化和正离子多重反应监测。结果：利多卡因房水浓度在2.070~10350 ng·mL-1范围内线性关系良好（r=0.9995）。单次给予新西兰兔受试制剂和参比制剂后,房水中利多卡因的Cmax分别为（10193±4535）ng·mL-1和（11046±2734）ng·mL-1,AUC0-8分别为7582 ng·h·mL-1和8125 ng·h·mL-1,t1/2分别为2.6 h和1.9 h,Tmax均为0.3 h。结论：盐酸利多卡因眼用凝胶受试和参比制剂在房水中药动学特征一致,眼部给药后利多卡因可快速穿透角膜到达房水,并在房水中达到较高的浓度。     

硫普罗宁眼用凝胶的生物利用度及抗白内障作用

目的考察硫普罗宁眼用原位凝胶生物利用度及抗白内障效果。方法采用连续取样技术,通过柱前衍生化方法考察药物在兔眼房水中的动力学行为。利用硒性白内障大鼠晶状体混浊度的裂隙灯图像分析,动态考察硫普罗宁眼用原位凝胶的抗白内障作用。结果高剂量组硫普罗宁原位凝胶药物-时间曲线下面积为水溶液组的1.58倍。硫普罗宁原位凝胶和水溶液均延缓白内障的发生时间,前者作用尤佳,晶状体混浊度仅达到12%。结论与水溶液相比,硫普罗宁原位凝胶可提高眼内生物利用度,明显延缓白内障形成。     

Determination of tamsulosin in human aqueous humor and serum by liquid chromatography-electrospray ionization tandem mass spectrometry

A simple, sensitive and selective LC-MS/MS method was developed for the determination of tamsulosin in human aqueous humor and serum to study the recently reported eye-related adverse effects of this alpha(1)-blocker drug. Aqueous humor samples were analyzed by direct injection, after addition of the internal standard, labetalol. Liquid-liquid extraction with ethyl acetate was used for serum sample preparation. The chromatographic separation was performed on a reversed phase column by gradient elution with acetonitrile -0.1% formic acid at a flow-rate of 0.2 ml/min. Detection and quantification of the analytes were carried out with a linear ion trap mass spectrometer, using positive electrospray ionization (ESI) and multiple reaction monitoring (MRM). The limit of quantification was 0.1 ng/ml for both aqueous humor and serum samples and linearity was obtained over the concentration ranges of 0.1-4.7 ng/ml and 0.1-19.3 ng/ml for aqueous humor and serum samples, respectively. Acceptable accuracy and precision were obtained for concentrations within the standard curve ranges. The method has been used for the determination of tamsulosin in aqueous humor and serum samples from patients that were on tamsulosin medication and underwent cataract surgery.     

The ocular penetration of levofloxacin 1.5% and gatifloxacin 0.3% ophthalmic solutions in subjects undergoing corneal transplant surgery

ABSTRACT

Objective: To compare corneal tissue and aqueous humor concentrations of levofloxacin 1.5% and gatifloxacin 0.3% ophthalmic solutions after topical dosing.

Research design and methods: This was a randomized, observer-masked, parallel-group, multicenter study. Fifty-nine subjects undergoing planned penetrating keratoplasty were randomly assigned to receive either levofloxacin 1.5% or gatifloxacin 0.3% as follows: one drop 15?min prior to surgery and a second drop 10?min before surgery. Corneal button and aqueous humor samples were collected during surgery and immediately stored at –70?°C. Levofloxacin and gatifloxacin concentrations were determined by high-pressure liquid chromatography and mass spectrometry.

Main outcome measures: Corneal tissue and aqueous humor concentrations of levofloxacin and gatifloxacin.

Results: Levofloxacin achieved statistically significantly higher concentrations in both corneal tissue and aqueous humor compared to gatifloxacin in patients undergoing penetrating keratoplasty. In corneal tissue the mean concentration of levofloxacin was 64.8 ± 123.4?µg/g vs. 7.0 ± 9.3?µg/g for gatifloxacin (p < 0.0001). Mean aqueous humor concentration of levofloxacin was 0.976 ± 2.215?µg/mL vs. 0.0523 ± 0.143?µg/mL for gatifloxacin (p = 0.0002).

Conclusions: The high concentrations of levofloxacin achievable in corneal tissue with topical dosing suggest that levofloxacin 1.5% should be a useful agent in the treatment of ocular bacterial infections. However, the corneal concentrations achieved in this study may not be representative of concentrations in patients using less frequent dosing.     

N-三甲基壳聚糖包衣维生素A阳离子脂质体原位凝胶的兔房水药动学研究

目的:比较N-三甲基壳聚糖(TMC60)包衣的维生素A棕榈酸酯(VAP)阳离子脂质体-原位凝胶(TMC60-VAPL-ISG组)与市售VAP凝胶(诺沛组)在兔眼房水的药物动力学.方法:采用自身对照,两种制剂滴用后,用HPLC法测定不同时间点的兔眼房水中的VAP浓度,用3P97软件拟合求得药动学参数.结果:用药0.25 h后,TMC60-VAPL-ISG组各时间点房水内药物浓度均明显高于诺沛组,房水药物浓度-时间曲线下面积(AUC0-24)也明显高于诺沛组(P<0.05).结论:TMC60-VAPL-ISG可明显延长药物在眼部的滞留时间,增加房水中药物浓度,显著提高VAP的眼部生物利用度.     

pH敏感型魟鱼软骨多糖眼用原位凝胶兔眼药动学及其抑制角膜新生血管的研究

目的：制备pH敏感型魟鱼软骨多糖眼用原位凝胶剂（RCG凝胶）并考察其兔眼药动学和抑制角膜新生血管作用。方法：以卡波姆940和HPMC（1∶4, w/w）为辅料制得pH敏感型原位凝胶。取健康家兔30只,向兔眼中滴入50 μL RCG凝胶,分别于给药10,30,60,120,180 min后处死家兔,收集兔眼玻璃体、房水、角膜和虹膜,并测定药物含量。取家兔20只,建立角膜新生血管模型并随机分为4组,分别给予生理盐水,25,50,100 mg·mL^-1 RCG凝胶。观察给药后第3,6,9,12天新生血管面积及角膜病理切片。结果：魟鱼软骨多糖在玻璃体、房水、角膜和虹膜的药动学均符合二室模型,在玻璃体、房水、角膜和虹膜中的C_max分别为（1.35±0.41）,（9.31±0.39）,（27.78±0.32）,（15.97±0.13） μg·mL^-1;AUC_0-180分别为（80.54±9.65）,（571.91±18.32）,（1 763.72±48.66）,（1 034.55±33.87） μg·mL^-1·min。对照组、低、中、高剂量组在第12天的新生血管面积分别为（30.00±3.45）,（24.31±3.12）,（5.36±1.24）,（4.89±1.09） mm²。角膜病理切片中,对照组和低剂量组中有大量炎性细胞浸润,新生血管较多;而中剂量和高剂量组中角膜中炎性细胞和新生血管明显较少。结论：制备了一种pH敏感型魟鱼软骨多糖眼用原位凝胶,该凝胶给药后在角膜部位具有最大的药物浓度,其给药剂量高于50 mg·mL^-1时,具有显著的抑制新生血管生成的作用,该原位凝胶剂具有较好的临床应用价值。