ABSTRACT The interaction of natamycin-azithromycin combination against 60 ocular fungal isolates was tested in vitro . The combination produced 100% synergistic interactions when natamycin was added to azithromycin 20, 40, and 50 μg/ml against Aspergillus flavus species complex (AFSC) isolates and to azithromycin 50 μg/ml against Fusarium solani species complex isolates. Addition of 50 μg/ml azithromycin enhanced natamycin's effect against AFSC isolates by reducing natamycin MIC 90 from 64 to 0.031 μg/ml. No antagonism was observed.

ABSTRACT The in vitro activities of amphotericin B in combination with rifampin were assessed against 95 ocular fungal isolates. The interactions between amphotericin B and rifampin at 4, 8, 16, and 32 μg/ml were synergistic for 11.8%, 51.0%, 90.2%, and 94.1%, respectively, of Fusarium solani species complex isolates and for 13.6%, 45.5%, 93.2%, and 95.5%, respectively, of Aspergillus flavus species complex isolates. Antagonism was never observed for the amphotericin B-rifampin combinations.

Reduction of intraocular pressure (IOP) by drugs is a major treatment for glaucoma. Clinically, diverse antiglaucoma drugs take effect to decrease the IOP through different mechanisms.However, due to limitations of traditional form of eye drops, the bioavailability of the drug and the patient compliance is lowered, the clinical efficacy is not good and also some toxic and side-effects come out.Otherwise, traditional medication is not suitable for neuroprotective drugs to work on both retina and optic nerve. Drug delivery system has the potential to improve the bioavailability of the drug, prolong the time of drug action, decrease the dosage and frequency of drugs, reduce the side-effects, and improve the patient compliance and efficacy.It is one of the most important studies in glaucoma medication development because it is valuable for patients' neuroprotection.Nowadays, several novel delivery systems have been designed. This review will focus on the progressions of some of the sustained-release antiglaucoma eye drops, polymeric gels, colloidal systems, membrane-controlled drug delivery system, ocular implants, and transscleral drug delivery systems.

Purpose To assess and compare the antifungal activity of polyhexamethylene biguanide (PHMB), thimerosal, cetylpyridinium chloride, and chlorhexidine, which are disinfectants used in multipurpose disinfectant solutions (MPDSs) against ocular pathogenic Fusarium solani and Aspergillus flavus isolates in vitro. Methods The in vitro activity of PHMB, thimerosal, cetylpyridinium chloride, and chlorhexidine was assessed against 40 isolates of ocular pathogenic fungi that included 24 F. solani and 16 A. flavus isolates. The strains were tested by broth dilution antifungal susceptibility testing of filamentous fungi approved by the CLSI (Clinical and Laboratory Standards Institute) M38-A document. Results MIC90 (minimum inhibitory concentration for 90% of the organisms) values of PHMB were 4 and 16 μg/mL for F. solani and A. flavus, respectively. MIC90 values of thimerosal were 0.0313 and 0.0625 μg/mL for F. solani and A. flavus, respectively. MIC90 values of cetylpyridinium chloride were 2 and 2 μg/mL for F. solani and A. flavus, respectively. MIC90 values of chlorhexidine were 32 and 32 μg/mL for F. solani and A. flavus, respectively. Conclusions As a disinfectant used in MPDSs, thimerosal showed the highest levels of antimicrobial activity against ocular pathogenic F. solani and A. flavus isolates. The concentrations of PHMB (0.0001%), cetylpyridinium chloride (0.00014%), and chlorhexidine (0.003%) in MPDSs are sublethal levels for ocular pathogenic F. solani and A. flavus isolates. Although multiple ingredients within MPDSs play a role in antimicrobial efficacy, antimicrobial activity may be significantly influenced by the disinfectants used in the solution formulations.

PURPOSE Fungal keratitis is emerging as a major cause of vision loss in a developing country such as China because of higher incidence and the unavailability of effective antifungals. It is urgent to explore broad-spectrum antifungals to effectively suppress ocular fungal pathogens, and to develop new antifungal eye drops to combat this vision-threatening infection. The aim of this study is to investigate the antifungal activity of silver nanoparticles (nano-Ag) in comparison with that of natamycin against ocular pathogenic filamentous fungi in vitro. METHODS Susceptibility tests were performed against 216 strains of fungi isolated from patients with fungal keratitis from the Henan Eye Institute in China by broth dilution antifungal susceptibility test of filamentous fungi approved by the Clinical and Laboratory Standards Institute M38-A document. The isolates included 112 Fusarium isolates (82 Fusarium solani species complex, 20 Fusarium verticillioides species complex, and 10 Fusarium oxysporum species complex), 94 Aspergillus isolates (61 Aspergillus flavus species complex, 11 Aspergillus fumigatus species complex, 12 Aspergillus versicolor species complex, and 10 Aspergillus niger species complex), and 10 Alternaria alternata isolates. The minimum inhibitory concentration (MIC) range and mode, the MIC for 50% of the strains tested (MIC50 value), and the MIC90 value were provided for the isolates with the SPSS statistical package. RESULTS MIC50 value of nano-Ag were 1, 0.5, and 0.5 μg/mL for Fusarium spp., Aspergillus spp., and Al. alternata, respectively. MIC90 values of nano-Ag were 1, 1, and 1 μg/mL for Fusarium spp., Aspergillus spp., and Al. alternata, respectively. MIC50 values of natamycin were 4, 32, and 4 μg/mL for Fusarium spp., Aspergillus spp., and Al. alternata, respectively. MIC90 values of natamycin were 8, 32, and 4 μg/mL for Fusarium spp., Aspergillus spp., and Al. alternata, respectively. CONCLUSIONS Nano-Ag, relative to natamycin, exhibits potent in vitro activity against ocular pathogenic filamentous fungi.

In the present study, the antifungal effects of phenylmercuric nitrate and benzalkonium chloride versus those of natamycin and ketoconazole were assessed against 216 filamentous fungi isolates from cases of fungal keratitis. They included 112 Fusarium isolates, 94 Aspergillus isolates, and 10 Alternaria alternata isolates. The strains were tested by broth dilution antifungal susceptibility testing of filamentous fungi approved by the Clinical and Laboratory Standards Institute M38-A document. The results showed that the MIC(50) values of phenylmercuric nitrate were 0.0156, 0.0156, and 0.0313 μg/mL for Fusarium spp., Aspergillus spp., and A. alternata, respectively. The MIC(90) values of phenylmercuric nitrate were 0.0313, 0.0313, and 0.0313 μg/mL for Fusarium spp., Aspergillus spp., and A. alternata, respectively. The MIC(50) values of benzalkonium chloride were 16, 32, and 8 μg/mL for Fusarium spp., Aspergillus spp., and A. alternata, respectively. The MIC(90) values of benzalkonium chloride were 32, 32, and 16 μg/mL for Fusarium spp., Aspergillus spp., and A. alternata, respectively. The study indicates that phenylmercuric nitrate has considerable antifungal activity and its effect is significantly superior to those of benzalkonium chloride, natamycin, and ketoconazole against ocular pathogenic filamentous fungi in vitro, deserving further investigation for treating fungal keratitis as a main drug.

To determine the antifungal activity of phenylmercuric acetate against ocular pathogenic fungi in vitro and develop new antifungal eye drops to combat keratomycosis.The in vitro activity of phenylmercuric acetate was assessed against 261 isolates of ocular pathogenic fungi that included 136 Fusarium spp. isolates, 98 Aspergillus spp. isolates, 10 Alternaria alternata isolates and 17 other pathogens. The activity of phenylmercuric acetate was compared with the activities of amphotericin B and natamycin. In vitro susceptibility testing was performed by broth microdilution assay, in accordance with the CLSI (formerly NCCLS) M38-A guidelines for filamentous fungi.MIC(90)s of phenylmercuric acetate were 0.0156, 0.0156, 0.0156 and 0.0156 mg/L for Fusarium spp., Aspergillus spp., A. alternata and other pathogens, respectively. MIC(90)s of amphotericin B were 2, 2, 1 and 1 mg/L for Fusarium spp., Aspergillus spp., A. alternata and other pathogens, respectively. MIC(90)s of natamycin were 8, 32, 4 and 4 mg/L for Fusarium spp., Aspergillus spp., A. alternata and other pathogens, respectively.Phenylmercuric acetate has promising antifungal activity, which is significantly superior to the activities of amphotericin B and natamycin against a wide variety of ocular pathogenic fungi based on comparative MIC values. Additional evaluation is required to determine its clinical utility.

The in vitro activity of nano-silver versus those of fluconazole and natamycin was assessed against 264 ocular fungal isolates. The activity of nano-silver against Fusarium spp., Aspergillus spp., and Alternariaalternata was 8 times, 32 times, and 2 times, respectively, greater than that of natamycin and 512times, 256 times, and 4 times, respectively, greater than that of fluconazole. Nano-silver's antifungalactivity was significantly superior to those of natamycin and fluconazole against ocular pathogenic fungi in vitro. [Chuanwen Gao, Yan Xu, Chao Xu. In Vitro Activity of nano-silver against Ocular Pathogenic Fungi. Life Sci J 2012;9(4):750-753] (ISSN:1097-8135). http://www.lifesciencesite.com. 117

Objective To observe the retinal toxicity of repeated intravitreal injection with bevacizumab(Avastin)in diabetic rats.Methods Forty male Sprague Dawley(SD)rats were randomly divided into normal group(Group A,10 rats)and diabetes mellitus group(30 rats).The rats in diabetes mellitus group were induced with streptozotocin injection for diabetic retinopathy model.And then randomly divided into diabetic retinopathy(DR)group(Group B,10 rats),the rats were not intervened;the left eyes of the other 20 rats were intravitreal injected with bevaeizumab 3 μ1(25 mg/m1)for 3 times as experimental group(Group C);the right eyes of the 20 rats were not intervened as experimental control group(Group D),20 days after last intravitreal injection,retinal function was measured by Flicker Electroretinogram (F-ERG);retinal vascular pattern was determined by fluorescence microscopy of ethidium bromide(EB)stained retinal flat mounts;retinal morphological changes were determined by light microscope on hematoxylin-eosin (HE) stained sections;Thy-1 and VEGF expression was measured by immunohistochemistry staining.Results F-ERG showed that-the differences of a-and b-waves-the b-wave amplitude and the Ops-wave amplitude in the implicit time between group A,B,C and D were significant (F=33.165,36.162,19.955,23.243;P=0.000);the differences of a-wave amplitude between group A,B,C and D was not significant(F=0.097,P=0v961).Retinal blood vessel pattern was normalin Group A;retinal vascular vessels were tortuous and irregularly expanded in Group B:retinal vascular vessels of Group C were regular and thinner than Group A;microaneurysm were showed in Group D.Light microscope displayed that the layers of the rat retina of Group A were regular,the retinal architectures of Group B were irregular,the retinal layers were regular in Group C,the retinal layers were irregular in Group D.Immunohistochemistry staining discovered that Thy-1 and VEGF were mainly expressed in ganglion cell layer(GCL).Conclusion Repeated intravitreal injection of bevacizumab iS toxic tO retina of diabetes mellitus rats.

OBJECTIVE:To investigate antifungal activity of butenafine in comparison with that of natamycin, amphotericin B and fluconazole against ocular pathogenic filamentous fungi in vitro.METHODS:It was an experimental study. Susceptibility tests were performed against 260 isolates of ocular pathogenic filamentous fungi by broth dilution antifungal susceptibility test of filamentous fungi approved by the Clinical and Laboratory Standards Institute (CLSI) M38-A document. The isolates included Fusarium spp. (136), Aspergillus spp. (98), Alternaria alternata (9), Curvularia lunata (3), and unusual ocular pathogens (14). Final concentration ranged from 0.008 to 16.000 mg/L for butenafine, from 0.031 to 16.000 mg/L for amphotericin B and natamycin, and from 0.5 to 256.0 mg/L for fluconazole. Following incubation at 35 degrees C for 48 h, minimal inhibitory concentration (MIC) was determined according to the CLSI M38-A document. For amphotericin B and natamycin, the MIC was defined as the lowest drug concentration that prevented any discernible growth. For butenafine and fluconazole, the MIC was defined as the lowest concentration in which an approximately 75% reduction compared to the growth of the control was observed. Candida parapsilosis ATCC22019 was used as quality control strains to validated the results. Mean MIC and MIC range, the MIC at which 50% of the isolates tested were inhibited (MIC(50)) and the MIC at which 90% of the isolates tested were inhibited (MIC(90)), were provided for all the isolates tested by using descriptive statistical analysis with the statistical SPSS package (version 13.0).RESULTS:MIC(90) of butenafine, natamycin, amphotericin B and fluconazole were 4, 8, 2 and 512 mg/L for Fusarium spp., respectively; 0.063, 32.000, 2.000 and 256.000 mg/L for Aspergillus spp., respectively; 0.5, 8.0, 2.0 and 128.0 mg/L for Alternaria alternate, respectively; 0.125, 2.000, 0.500 and 4.000 mg/L for Curvularia lunata, respectively; and 1, 4, 1 and 256 mg/L for unusual ocular pathogens, respectively.CONCLUSIONS:Butenafine exhibits potent antifungal activity against a wide variety of ocular pathogenic fungi, especially for Aspergillus spp., Alternaria alternata, Curvularia lunata, and some unusual ocular pathogens and may have a role in future studies of antifungal eye drops and treating fungal keratitis.

The in vitro activity of thimerosal versus those of amphotericin B and natamycin was assessed against 244 ocular fungal isolates. The activity of thimerosal against Fusarium spp., Aspergillus spp., and Alternaria alternata was 256 times, 512 times, and 128 times, respectively, greater than that of natamycin and 64 times, 32 times, and 32 times, respectively, greater than that of amphotericin B. Thimerosal's antifungal activity was significantly superior to those of amphotericin B and natamycin against ocular pathogenic fungi in vitro.

ABSTRACT The in vitro activity of the silver nitrat e was assessed in comparison with that of natamycin against 128 corneal Fusarium isolates and 90 corneal Aspergillus isolates. MIC 90 s of silver nitrat e were 2 μg/ml for Fusarium spp. and 1 μg/ml for Aspergillus spp. MIC 90 s of natamycin were 8 μg/ml for Fusarium spp. and 32 μg/ml for Aspergillus spp. Silver nitrat e exhibited potent antifungal activity against ocular fungi in vitro.

OBJECTIVE:To investigate antifungal activity of silver nitrate compared with fluconazole, ketoconazole and amphotericin B against ocular pathogenic fungi in vitro.METHODS:It was an experimental study. Susceptibility tests were performed against 260 isolates (15 genera and 29 species) of ocular pathogenic fungi by broth dilution antifungal susceptibility testing of filamentous fungi (M38-A) approved by National Committee for Clinical Laboratory Standards (NCCLS). Final concentrations ranged from 0.031 to 16.000 mg/L for silver nitrate, ketoconazole and amphotericin B, from 0.5 - 256.0 mg/L for fluconazole. Minimum inhibitory concentration (MIC) was defined as the lowest drug concentration that showed absence of growth or complete growth inhibition (100%). The end points were determined as 100% growth inhibition for silver nitrate and amphotericin B, and > or = 75% growth inhibition for ketoconazole and fluconazole.RESULTS:The MICs at which 90% of isolates were inhibited (MIC(90)) of silver nitrate, ketoconazole, amphotericin B and fluconazole were 2.000, 512.000, 32.000 and 2.000 mg/L for Fusarium species, respectively; 1.000, 256.000, 2.000 and 2.000 mg/L for Aspergillus species, respectively; 2.000, 128.000, 4.000 and 2.000 mg/L for Alternaria alternate, respectively; 2.000, 4.000, 0.125 and 0.500 mg/L for Curvularia lunata, respectively; and 1.000, 256.000, 1.000 and 1.000 mg/L for unusual ocular pathogens, respectively. Silver nitrate was highly active against Aspergillus species (92.9% susceptible at a MIC of < or = 1.0 mg/L) and Fusarium species (96.3% susceptible at a MIC of < or = 2.0 mg/L). 95.6% of Fusarium species and 90.8% of Aspergillus species exhibited resistance to fluconazole, 44.1% of Fusarium species and 42.9% of Aspergillus species exhibited resistance to amphotericin B, 66.2% of Fusarium species exhibited resistance to ketoconazole. The activity of silver nitrate against the fluconazole-resistant, ketoconazole-resistant and amphotericin B-resistant strains was high.CONCLUSION:Silver nitrate has promising activity against a wide variety of ocular pathogenic fungi in vitro, and may have a role in future studies of antifungal eye drops and treating fungal keratitis.

OBJECTIVEThe influence of an antioxidant, propyl gallate (PG), on the activity of amphotericin B (AMB), terbinafine (TBF), butenafine (BTF) and ketoconazole (KCZ) against ocular pathogenic filamentous fungi in vitro was investigated to determine whether PG could increase the antifungal activity.METHODSSusceptibility tests were performed against 6 isolates of ocular pathogenic filamentous fungi (Fusarium solanae, Fusarium moniliforme, Fusarium poae, Fusarium oxysporum, Aspergillus fumigatus and Aspergillus flavus) and 2 quality control strains (Candida krusei ATCC 6258 and Cadida parapsilosis ATCC 22019) by the NCCLS M38-P broth microdilution method (MIC). PG was added to the incubation media at a final concentration of 400 microg/ml. Antifungal agents were serially two-fold diluted and final dilutions were made in 1640 and PG-1640 culture media to a concentration ranging from 0.0313 to 16 microg/ml for AMB, TBF, BTF and KCZ. One hundred microl of the corresponding diluted inoculum suspension was added to each well of the microdilution tray. The MIC end-point of AMB was determined as 100% growth reduction and the MIC end-point of TBF, BTF, KCZ and PG was determined as 75% growth reduction as compared with the turbidity produced by the control well.RESULTSAt a concentration of 400 microg/ml, PG did not show any antifungal activity under these experimental conditions. The combination of PG (400 microg/ml) with amphotericin B revealed a remarkably increased activity against all of the isolates of ocular pathogenic filamentous fungi and quality control strains. In the combination of PG with terbinafine, a remarkably increased activity was observed against Fusarium solanae, Fusarium poae, Fusarium oxysporum, Aspergillus fumigatu and Aspergillus flavus. The combination of PG with butenafine had remarkably synergistic effect against Fusarium solanae, but did not synergistic or even showed antagonistic effect for other isolates. The combination of PG with ketaconazole was synergistic against Fusarium solanae, but was antagonistic against all other isolates.CONCLUSIONSCombination of PG and amphotericin has remarkably synergistic effect against all tested ocular pathogenic filamentous fungi isolates. Combination of PG and terbinafine has remarkably synergistic effect against some isolates. The PG-amphotericin combination and the PG-terbinafine combination may have a role in future studies of antifungal eye drops.

目的观察不同种类的穿透促进剂对乙酰唑胺滴眼液的眼内通透性作用.方法每次给兔滴药50 μL,30 min后抽取房水并进行反相高效液相色谱分析,计算房水中乙酰唑胺的质量浓度.结果1%、3.3%、10%乙酰唑胺滴眼液滴眼后30 min,前房药物质量浓度分别为( 0.073±0.013) μg/mL、(0.250±0.075) μg/mL、(0.032±0.074) μg/mL.与对照组相比,0.01%苯扎溴铵,1%甲基纤维素,1%、5%正丁醇以及5%、10%、20%二甲基亚砜均不能提高房水中乙酰唑胺的质量浓度(P＞0.05).0.012 5%～0.4%氮酮均可促进乙酰唑胺的眼内吸收,分别可提高前房药物质量浓度5.8～38.7倍(P＜0.01).此外,氮酮质量浓度和其对应的房水乙酰唑胺质量浓度的关系呈正相关(r= 0.92,P＜0.05).结论选择性地应用穿透促进剂可提高乙酰唑胺的眼内通透性.

OBJECTIVE:To compare the pharmacokinetics of 0.5% pilocarpine containing sodium hyaluronate with 1% generic pilocarpine solution.METHODS:One hundred albino rabbits were divided into 20 groups, each consisting of 5 animals. Ten groups received 0.5% pilocarpine containing sodium hyaluronate and 10 groups received 1% generic pilocarpine solution as control. The aqueous humor was withdrawn at 5, 10, 20, 30, 40, 60, 90, 120, 150, and 180 min after instillation. The drug was extracted from aqueous humor with dichloromethane and was detected by reversed phase high performance liquid chromatography (HPLC).RESULTS:The average recovery rate of pilocarpine from aqueous humor was 98.2%. The minimum detectable concentration was 0.025 micro g/ml. The peak concentration and half-life of pilocarpine in aqueous humor were 4.46 micro g/ml at 10 min and 31.83 min, respectively, in the experimental group. Whereas, the peak concentration and half-life of pilocarpine in aqueous humor were 2.25 micro g/ml at 20 min and 22.98 min, respectively, in the control group. The peak concentration of pilocarpine in aqueous humor in the experimental group was 1.98 (P < 0.05) times higher than the control group. The area under curve of the drug concentration-time (AUC(0 - 180)) in the experimental group was 1.75 times higher than the control group.CONCLUSION:Pilocarpine (0.5%) containing sodium hyaluronate significantly increased the peak concentration of pilocarpine, shortened the time of reaching peak concentration and prolonged the half-life in aqueous humor. These results indicate that 0.5% pilocarpine with sodium hyaluronate significantly increases ocular bioavailability of pilocarpine.

目的 评价两种自制的增效酮康唑滴眼液及酮康唑混悬滴眼液体外抗眼科丝状真菌活性.方法用微量液基稀释法测定两种增效酮康唑滴眼液及酮康唑混悬滴眼液对4株眼科常见致病丝状真菌(串珠镰刀菌、烟曲霉菌、黄曲霉菌及黑曲霉菌)的最低抑菌浓度(MIC),用二甲基亚砜(DMSO)溶解的酮康唑液做对照.结果增效酮康唑滴眼液Ⅰ、增效酮康唑滴眼液Ⅱ、酮康唑混悬滴眼液及DMSO溶解的酮康唑液对串珠镰刀菌的MIC分别为2、1、16、2μg/mL;对烟曲霉菌的MIC分别为0.5、0.5、2、0.5μg/mL;对黄曲霉菌的MIC分别为16、16、128、16μg/mL;对黑曲霉菌的MIC分别为0.25、0.25、4、0.25μg/mL.上述结果显示3种酮康唑滴眼液及DMSO溶解的酮康唑液对黑曲霉菌的作用最强,对烟曲霉菌、串珠镰刀菌的作用依次递减,对黄曲霉菌的作用较弱.两种增效酮康唑滴眼液的作用强度与DMSO溶解的酮康唑液的相似,三者的抗真菌活性均明显强于酮康唑混悬滴眼液.结论两种增效酮康唑滴眼液对4株眼科常见致病丝状真菌的体外抗真菌活性较酮康唑混悬滴眼液的明显增强,说明增加酮康唑的溶解度可明显增加其抗真菌活性。

OBJECTIVE:To establish models of experimental glaucoma in rabbits to investigate the treatment of glaucoma.METHODS:Twenty-one normal albino rabbits weighing 2.5 - 3.0 kg were studied. The rabbits were divided randomly into 4 groups: I, II, III and IV. Anterior chamber injection of 0.1 ml of 0.3% carbomer (I), 0.2 ml of methylcellulose (II), 0.2 ml of compound methylcellulose (III) and subconjunctival injection of 5 mg of dexamethasone (IV) were performed respectively on them to induce glaucoma. The intraocular pressure (IOP) was monitored with a Tono-pen XL tonometer several times prior to injection and 2 times per week after injection. The basic IOP in every group served as control.RESULTS:Experimental glaucoma occurred in eleven of twelve eyes in group I and IOP lasted from 20 to 50 days. The mean IOP levels were 29 - 35 mmHg (1 mm Hg = 0.133 kPa) and the peak IOP levels were 37 - 45 mm Hg. The IOP in 2 out of 10 eyes in group II increased to 22 - 50 mm Hg and lasted for 3 days. The IOP of 1 out of 10 eyes in group III increased to 25 - 40 mm Hg and lasted for 4 days. The IOP in eyes of group IV increased only 3 mmHg in the mean and lasted for one week. According to the standard, IOP above 22 mmHg for one week as the successful experimental glaucoma, group II and III were not the ideal ones and group IV was a failure.CONCLUSION:Experimental glaucoma model induced by carbomer has the advantages of producing moderate and sustained IOP elevation. The model is easy to be carried out. It is simple, reliable, and useful for investigating optic nerve and retinal damage in glaucoma and testing the toxicity and efficacy of various therapies.

OBJECTIVETo assess the effects of pilocarpine (PC) incorporated into an in situ gelling vehicle, submicron emulsion vehicle, polyvinyl alcohol vehicle and PC solution on intraocular pressure (IOP) in rabbits with carbomer-induced elevation of IOP.METHODSForty-three rabbit eyes with carbomer-induced elevation of IOP were randomly divided into 5 groups. Each eye in every group received topical application of PC from one of the ophthalmic formulations. IOP was measured before and 1, 2, 3, 4, 5, 7, 10, 12, 22 and 24 hours (h) after topical ocular administration of the ophthalmic formulations.RESULTSThe reduction in IOP lasted for 7 h and the maximum decrease was (12.25 +/- 5.28) mm Hg in the hypertensive eyes treated by 2% PC solution. The reduction in IOP lasted for 12 h and the maximum decrease was (13.67 +/- 4.61) mm Hg in the hypertensive eyes treated by 2% PC gel. The reduction in IOP lasted for 24 h and the maximum decrease was (13.63 +/- 3.58) mm Hg in the hypertensive eyes treated by 4% PC gel. The reduction in IOP lasted for 12 h and the maximum decrease was (13.55 +/- 3.90) mm Hg in the hypertensive eyes treated by 2% PC submicron emulsion. The reduction in IOP lasted for 10 h and the maximum decrease was (10.89 +/- 4.04) mm Hg in the hypertensive eyes treated by 2% PC polyvinyl alcohol. The duration of action for lowering IOP lasted longer following administration with new ophthalmic formulations as compared to 2% PC solution. The series of prolongation is as follows: 4% PC gel > 2% PC gel = 2% PC submicron emulsion > 2% PC polyvinyl alcohol > 2% PC solution. The maximum reduction in IOP was not significantly different among the groups. No clinical evidence of ocular toxicity occurred in all groups except mild conjunctival injection.CONCLUSIONThese results indicate that the duration of action for lowering IOP is longer in PC gel, PC submicron emulsion and PC polyvinyl alcohol as compared to PC solution. The duration of action with 4% PC gel lasts the longest among all the groups. A single dose of 4% PC gel applied once daily can reduce IOP for 24 h.

Objective To develop a rapid，sensitive and reliable high-performance gas chromatography to evaluate the fluconazole (FCZ) bioavailability after topically applied FCZ in-situ gelling ophthalmic delivery system to the rabbit eyes.Methods A megabore capillary column（30m long and inner diameter of 0.530 mm） with a 0.88-μm-thick bonded liquid phase was used.Detector was nitrogen-selective type.Tears adsorbed to the filter paper was directly by methanol with no evaporation stage prior to analysis.Aqueous humors was extracted by ethyl acetate.Results The duration of each analysis was less 10 min and the minimum detectable concentration was 0.01μg/ml.The assay was linear from 0.1 to 20 μg/ml.The average recoveries from tears and aqueous humors were 99.0% and 94.8%，respectively.Conclusion This method can be used to determine rabbit tears and aqueous humors levels of fluconazole and was practicable approach for evaluating intraocular pharmacokinetics after topically applied to rabbit eyes.