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We aimed to quantify the penetration of ciprofloxacin, ofloxacin, and moxifloxacin into the cornea and aqueous humor of cadaver eyes. A total of 60 enucleated eyes, not eligible for corneal transplantation, were divided into three groups and immersed in commercial solutions of 0.3% ciprofloxacin, 0.3% ofloxacin, or 0.5% moxifloxacin for 10 min. Whole corneas and samples of aqueous humor were then harvested and frozen, and drug concentrations analyzed by liquid chromatography tandem mass spectrometry. The mean corneal concentration of moxifloxacin was twice as high as ofloxacin, and the latter was twice as high as ciprofloxacin. The mean concentration of moxifloxacin in the aqueous humor was four times higher than the other antibiotics, and the mean concentrations of ciprofloxacin and ofloxacin were statistically similar. The amount of drug that penetrated the anterior chamber after a 10-min immersion was far below the safe limit of endothelial toxicity of each preparation. Moxifloxacin demonstrated far superior penetration into the cornea and anterior chamber of cadaver eyes compared to ciprofloxacin and ofloxacin. One should not expect endothelial toxicity with the commercial eye drops of ciprofloxacin, ofloxacin, and moxifloxacin that reach the anterior chamber through the cornea.

Purpose: To investigate the comparative penetration of 0.3% levofloxacin eye drops into the aqueous humour between cataract patients with or without (control) thin-wall filtering blebs., Methods: One drop of 0.3% levofloxacin was administered to the eyes at 30-min intervals for 3.5 h before phacoemulcification for both groups. Aqueous humour samples (0.1-0.2 ml) were aspirated during surgery. The concentration of levofloxacin in the aqueous humour was determined by high-performance liquid chromatography. The Student's t-test, Pearson correlation, and chi(2) test were used to compare the data of the two groups. A P<0.05 was required for results to be considered statistically significant., Results: The levofloxacin concentration in the aqueous humour was significantly increased (P<0.0001) in the bleb (mean+SD: 3.7+/-2.3 microg/ml) vscontrol group (0.4+/-0.2 microg/ml). Intraocular pressure and the bleb area were not correlated with levofloxacin concentration., Conclusion: The presence of thin-wall filtering blebs increases intraocular penetration of topically administered levofloxacin.

Background/aims: To compare the penetration of levofloxacin, ofloxacin and ciprofloxacin in the aqueous humour of eyes with functioning filtering blebs., Methods: In this investigator-masked study, 48 patients with functioning filtering blebs requiring cataract surgery were randomised into six groups of eight patients. Groups 1, 2 and 3 received topical ofloxacin 0.3% (Ocuflox), ciprofloxacin 0.3% (Ciloxan) and levofloxacin (Quixin) respectively; Groups 4, 5 and 6 received the same treatment with the corresponding oral dose of ofloxacin 400 mg (Floxin), ciprofloxacin 400 mg (Cipro) and levofloxacin 250 mg (Levaquin). Aqueous antibiotic levels were determined by mass spectrometry of aqueous samples from each patient., Results: The mean aqueous level for topical levofloxacin was significantly higher than those achieved by topical ofloxacin or ciprofloxacin (p value = 0.02 and 0.01, respectively). The combination of topical and oral levofloxacin was significantly higher than topical levofloxacin alone (p = 0.05) and the ciprofloxacin combination (p = 0.003) but not significantly higher than the ofloxacin combination therapy., Conclusions: Topical levofloxacin penetrates better than ofloxacin or ciprofloxacin into the aqueous of eyes with functioning filtering blebs. The combination of topical and oral levofloxacin may be preferable in the treatment of bleb-associated infections (NCT 00392275; Clinical trials.gov).

Purpose: To investigate the penetration of ofloxacin and moxifloxacin into the aqueous and vitreous after topical administration one hour before vitrectomy surgery., Design: Prospective, randomized, double-blind case series study., Methods: Twenty-seven patients undergoing vitrectomy were randomized to receive either topical ofloxacin 0.3% or moxifloxacin 0.5% every 10 minutes for one hour before surgery. Aqueous and vitreous samples were obtained and analyzed using high-performance liquidation chromatography., Results: The moxifloxacin aqueous (1.576 +/- 0.745 microg/ml) and vitreous (0.225 +/- 0.013 microg/ml) levels were significantly higher than the ofloxacin aqueous (0.816 +/- 0.504 microg/ml) (P = .0009) and vitreous (0.225 +/- 0.013 microg/ml) [P = .0054] levels, respectively. The mean moxifloxacin aqueous and vitreous levels exceeded the minimum inhibitory concentration for 90% of isolates (MIC(90)) for a wide variety of bacteria implicated in endophthalmitis. In contrast, the aqueous level of ofloxacin exceeded the MIC(90) of only a few organisms., Conclusions: Moxifloxacin applied every 10 minutes during the hour before vitrectomy penetrated the eye significantly better than ofloxacin.

Purpose: To investigate the aqueous and vitreous penetration of levofloxacin, the drug was administered topically and/or orally to patients undergoing vitrectomy., Methods: Thirty-six patients undergoing initial vitrectomy with phacoemulsification and aspiration (PEA) were enrolled, and were divided randomly into three groups. Group 1 was treated with topical application of levofloxacin (three times on the day before surgery and seven times on the day of surgery), Group 2 received oral administration of levofloxacin (200 mg twice on the day before surgery and 200 mg at 3 hours before surgery), and Group 3 received both topical and oral levofloxacin according to the above schedules. The concentration of levofloxacin was measured in aqueous humor and vitreous fluid samples obtained during surgery., Results: In Groups 1, 2, and 3, the mean levofloxacin concentration in aqueous humor was 0.765+/-0.624 micro g/mL, 1.279+/-0.440 micro g/mL, and 1.823+/-0.490 micro g/mL, respectively, while the mean levofloxacin concentration in vitreous fluid was <0.02 micro g/mL, 1.455+/-0.445 micro g/mL, and 1.369+/-0.530 micro g/mL, respectively., Conclusions: Oral administration of levofloxacin at a dose of 400 mg/day was sufficient for the prophylaxis of ocular infections, because the drug concentrations in both aqueous humor and vitreous fluid were higher than the MIC90 values for major ocular pathogens. Topical application of levofloxacin achieved adequate drug levels in aqueous humor, but not in vitreous fluid, while combined topical and oral administration had an additive effect on the drug concentration in aqueous humor.

Intraocular levels of ofloxacin are documented after topical and systemic administration, but systemic administration of ofloxacin in ocular compression has not yet been studied. This study was undertaken to determine the intraocular penetration of systemic ofloxacin into aqueous and vitreous humor after the application of ocular compression in rabbit eyes. Ocular compression with the Honan balloon was applied for 30 min to the right eyes of 11 albino New Zealand white rabbits. After the application of ocular compression, 2 mg/mL of ofloxacin was administered intravenously. Samples from aqueous and vitreous humor were collected 30 min after infusion. Ofloxacin concentrations were determined through high-performance liquid chromatography. The mean aqueous level of ofloxacin was significantly higher in the compression group (2.40+/-1.00 microg/mL) than in the no-compression group (1.61+/-1.06 microg/mL) (P<.05). The mean vitreous concentrations of ofloxacin were 0.70+/-0.33 microg/mL and 0.50+/-0.18 microg/mL in the compression and no-compression groups, respectively. A significant difference was observed between vitreous levels of ofloxacin in the compression and no compression groups (P<.05). Ocular compression enhanced the penetration of ofloxacin in both aqueous and vitreous humor. The drug level in the aqueous humor was sufficient for the minimum inhibitory concentration for 90% of isolates (MIC90) to inhibit most microorganisms. Although the mean vitreous ofloxacin concentration was increased by previous ocular compression, it was not sufficiently above the MIC90 for most ocular pathogens that caused endophthalmitis.

In the study presented here, levofloxacin concentrations in serum samples and the aqueous humour (AH) of 16 patients undergoing cataract extraction were measured in order to determine the penetration characteristics of levofloxacin into the AH of the non-inflamed human eye. Cataract removal was performed at various times (from 90 to 270 min) after the end of a 30-min intravenous infusion of 500 mg of levofloxacin. Serum samples were obtained 1 h after the end of levofloxacin administration (Cmax); AH and a second serum sample were taken simultaneously during the operation, and the concentrations of levofloxacin in AH (C(AH)) and serum (C(S)) were determined using a rapid high-performance liquid chromatography assay. The mean Cmax was 6.07 microg/ml (range 3.75-9.53 microg/ml, SD 1.83). The mean C(AH) at the first hour following levofloxacin administration was 1.37 microg/ml (range 1.17-1.6 microg/ml, SD 0.22) and the mean ratio (R=C(AH)/C(S)) was 0.26 (range 0.24-0.3, SD 0.02). The mean C(AH) at 125-270 min following levofloxacin administration was 1.39 microg/ml (range 0.82-1.98 microg/ml, SD 0.33) and the mean R was 0.3 (range 0.15-0.53, SD 0.11). Of 16 patients, 15 had a C(AH) of >1 microg/ml 1 h after levofloxacin administration. In conclusion, 1 h after administration of 500 mg of levofloxacin, the levels obtained were higher than the MIC at which 90% of methicillin-susceptible Staphylococcus aureus and certain gram-negative bacteria strains are inhibited.

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.

The ocular disposition of levofloxacin in patients receiving two 500-mg oral doses 10 h apart before cataract surgery was assessed with the intent of defining drug ocular exposure over time. The mean aqueous humor concentrations persisted above 1.5 mg/liter between 1.5 and 6.0 h after the second dose, with average aqueous-to-plasma ratios ranging between 0.33 and 0.57. This favorable ocular disposition provides support for trials of systemic levofloxacin for prophylaxis of postoperative endophthalmitis in selected patients or as adjunctive therapy for the treatment of this potentially devastating infective complication.

Aims: We intravenously administered flomoxef sodium (FMOX) 120 minutes before cataract surgery, topically administered levofloxacin (LVFX) into the eyes four times at 30-minute intervals before surgery, and measured the aqueous humor concentrations of these agents to investigate their penetration into the aqueous humor and their efficacy in the prevention of postoperative endophthalmitis., Methods: Sixty-eight patients who underwent cataract surgery at the Department of Ophthalmology, Yokohama City University School of Medicine, or its affiliate, Kanazawa Hospital, Yokohama, were enrolled in this study. They received one or both of the following: 1.0 g FMOX via a 20-minute intravenous drip and LVFX ophthalmic solution applied four times at 30-minute intervals, both beginning two hours before the operation. Aqueous humor was aspirated from the anterior chamber and assayed for FMOX and LVFX concentrations using high-performance liquid chromatography (HPLC)., Results: The mean intraoperative FMOX and LVFX concentrations in the patients' aqueous humor were 1.21 +/- 0.63 microg/ml and 0.69 +/- 0.47 microg/ml, respectively. These concentrations sufficiently exceeded the MIC90 values against Staphylococcus epidermidis, S. aureus, and Propionibacterium acnes., Conclusions: The FMOX and LVFX concentrations in the aqueous humor sampling were adequate to kill bacteria in vitro. These drugs may have efficacy in the prevention of postoperative endophthalmitis in patients undergoing cataract surgery.

The aqueous penetration of the commercial preparations of the fluoroquinolone antibiotics ofloxacin, ciprofloxacin, levofloxacin, and gatifloxacin were compared following topical dosing in a rabbit model. Levofloxacin achieved the highest aqueous concentrations, with a mean aqueous level of 4.8014 microcg/mL (p = 0.002, p = 0.00002, p = 0.015.) Ofloxacin (2.5136 microcg/mL) and gatifloxacin (2.4817 microcg/mL) achieved statistically equal aqueous concentrations (p = 0.479). Ciprofloxacin reached the lowest levels in the aqueous humor (0.9616 microcg/mL, p = 0.00002, 0.00004, 0.008). Gatifloxacin alone achieved concentrations in excess of the MIC90s of gram-positive pathogens of concern.

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.

Purpose: Pharmacokinetic studies of antibacterial agents for infectious eye diseases have usually been performed on normal rabbit eyes. In this study, the intraocular penetration of fluoroquinolone ophthalmic solutions was determined in normal rabbit eyes and in rabbit eyes that had the corneal epithelium intentionally removed., Methods: We determined the intraocular penetration of ofloxacin (OFLX), levofloxacin (LVFX), and norfloxacin (NFLX), fluoroquinolone ophthalmic solutions that are already on the market and undergoing clinical studies, by injecting 50 microl of each solution into the cul-de-sacs of rabbit eyes three times at 15-min intervals. The drug concentration at 10, 30, 60, 120, and 240 min after final instillation was determined by high-performance liquid chromatography., Results: The maximum concentration in the aqueous humor of normal rabbit eyes was 2.09 +/- 1.56 microg/ml (60 min, OFLX), 2.57 +/- 1.00 microg/ml (30 min, LVFX), and 0.42 +/- 0.12 microg/ml (120 min, NFLX). The drug concentration in the aqueous humor of eyes with intentionally removed corneal epithelium was 12.50 +/- 5.62 microg/ml (30 min, OFLX), 9.02 +/- 2.45 microg/ml (60 min, LVFX), and 8.54 +/- 5.17 microg/ml (30 min, NFLX). The drug penetration of the eye drops into eyes with removed corneal epithelium was around 6 times (OFLX), 3.5 times (LVFX), and 20 times (NFLX) higher than the penetration into the eye with normal cornea., Conclusion: Among the pharmacokinetic parameters of the three ophthalmic solutions according to the one-compartment model, the maximum concentration in the aqueous and the area under the concentration-time curve in the aqueous tended to be higher in the eyes with intentionally removed corneal epithelia than in those with normal corneas.

Purpose: To compare aqueous humor concentrations of levofloxacin vs ciprofloxacin when used as prophylactic medications before phacoemulsification., Design: Patients (n = 93) were randomly assigned to receive either 0.5% levofloxacin (Quixin) or 0.3% ciprofloxacin (Ciloxan) using one of the following dosing regimens: (A) 1 to 2 drops four times a day for 2 days preoperatively; (B) 5 doses (1 to 2 drops) delivered every 10 minutes in the hour immediately preceding surgery; or (C) the combination of A and B., Methods: Aqueous samples (0.1 ml) were obtained immediately before surgery, and drug concentrations were measured using high performance liquid chromatography/mass spectrometry., Results: The mean concentration of levofloxacin in the aqueous humor was significantly greater than that of ciprofloxacin in all treatment groups (P <.001): 284.8 vs 67.4 microg/ml (regimen A); 1,135.6 vs 185.6 microg/ml (regimen B); and 1,618.6 vs 241.5 (regimen C). Dosing regimen B delivered significantly more drug to the aqueous humor than regimen A for both levofloxacin (P < or =.001) and ciprofloxacin (P =.004). Dosing regimen C delivered significantly more drug to the aqueous humor than regimen B for levofloxacin (P =.05) but not for ciprofloxacin (P =.384)., Conclusions: Although the concentration of active drug in levofloxacin is approximately 1.7-fold higher than that in ciprofloxacin, the aqueous concentration of levofloxacin after topical administration was four to seven times greater than ciprofloxacin; these differences were statistically significant. With dosing regimens B and C, levofloxacin concentrations in the aqueous humor were above the MIC90 for most common ocular pathogens, including Staphylococcus and Streptococcus species. Ciprofloxacin did not reach such concentrations in any treatment group.

Purpose: To compare aqueous humour levels of levofloxacin and ciprofloxacin following topical application to patients scheduled for cataract surgery., Methods: A total of 59 patients undergoing cataract surgery were randomly assigned to topical treatment with either levofloxacin 0.5% or ciprofloxacin 0.3% eye drops, at one drop every 15 min for four doses immediately prior to surgery. Aqueous humour samples were collected by paracentesis and analysed for drug content., Results: The (geometric) mean aqueous humour concentration of levofloxacin was 0.728 microg/ml; that of ciprofloxacin was 0.080 microg/ml., Conclusions: Levofloxacin achieves 9.1 times the aqueous humour concentration of ciprofloxacin. It could be considered a better choice than ofloxacin or ciprofloxacin for topical ophthalmic use.

Objective: To compare the aqueous humor penetration of topically applied ofloxacin, ciprofloxacin and tobramycin in human eyes., Methods: Senile cataract patients (125 eyes in 125 cases) receiving phacoemulsification were randomized into three groups: ofloxacin, 42 eyes; ciprofloxacin, 41 eyes and tobramycin, 41 eyes. Each group was randomized into five sub-groups, with 8 or 9 eyes in each sub-group. Each group received either 0.3% ofloxacin, ciprofloxacin or tobramycin topical drops preoperatively. Eyedrops were instilled one drop every 15 minutes for six times. Aqueous samples were obtained from different sub-groups during surgery, 7.5, 15.0, 30.0, 60.0 and 120.0 min after the last drop, respectively. Concentration of the antimicrobial agents was determined by the HPLC (high pressure liquid chromatography)., Results: Aqueous humor concentration of ofloxacin was significantly higher than that of ciprofloxacin at the same period after the last drop. The bioavailability of ofloxacin was 6 times that of ciprofloxacin. Tobramycin could not be detected by HPLC, so its concentration was lower than the minimum detectable level by HPLC (0.05 micro g/ml)., Conclusion: Ofloxacin has the best aqueous penetration in human eyes, as compared with ciprofloxacin and tobramycin, which suggests ofloxacin could be the preferred topical medicine for the prevention and treatment of endophthalmitis.

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.

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.

This study was designed to measure the concentration of levofloxacin in aqueous humor after topical and oral administration in patients undergoing cataract extraction. Patients were randomly divided into four groups. Levofloxacin concentration in the aqueous humor was the highest in the group in which 600 mg was given orally plus five topical instillations before surgery. The aqueous humor levels of levofloxacin after topical and oral administration exceeded the minimum inhibitory concentrations for certain bacterial species that frequently cause intraocular infection., (Copyright 2003 S. Karger AG, Basel)

Ocular penetration of two topical antibiotics used to treat bacterial conjunctivitis was assessed in adult volunteers scheduled for cataract surgery. In this randomized, parallel-group study, patients instilled trimethoprim sulfate 0.1%/polymyxin B (n = 23) or ofloxacin 0.3% (n = 25) QID for 3 days, plus 4 instillations in the hour before surgery. Analysis of aqueous humor samples obtained during surgery showed a 2.4-fold greater concentration of ofloxacin over trimethoprim (1.135 micro g/ml vs 0.470 micro g/ml; P <.0001). The greater concentration of ofloxacin in ocular tissue coupled with its superior antibacterial activity profile supports its use as an alternative to trimethoprim/polymyxin B for treatment of bacterial conjunctivitis.

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.

Purpose: In order to determine whether the one-component method for calculating drug concentration in the aqueous(AQCmax) is useful for selecting an appropriate ophthalmic solution, 6 general purpose antimicrobial ophthalmic solutions already on the market were investigated., Methods: The drugs examined were levofloxacin (LVFX), chloramphenicol(CP), erythromycin lactobionate(EM), micronomicin sulfate(MCR), cefmenoxime hydrochloride(CMX) and disodium sufobenzyl penicillin(SBPC). Fifty microliters of each solutions was instilled into the cul-de-sac of New Zealand White rabbit eyes 3 times at 15-minute intervals. The drug concentrations in(the anterior sac aqueous,: this is wrong) the aqueous humor 10, 30, 60, 120 and 240 minutes after the final instillation were examined by high performance liquid chromatography(HPLC) and/or bioassay. The AQCmax was calculated using the one-compartment method., Results: The calculated AQCmax was 2.5 micrograms/ml (HPLC method) and 2.28 micrograms/ml (Bioassay Method) for LVFX, 2.17 micrograms/ml for CP, and 0.45 microgram/ml for EM. The AQCmax for CMX, MCR and SBPC could not be calculated by the one-compartment method., Conclusion: The AQCmax of LVFX was higher than that of the 2 other general purpose antimicrobial ophthalmic solutions. The AQCmax of these drugs might be a useful parameter for selecting an appropriate ophthalmic solution for the treatment of infected eyes.

Purpose: To evaluate the penetration of ciprofloxacin, levofloxacin, and moxifloxacin into the aqueous humor after oral administration., Setting: Alcorcon Hospital, Madrid, Spain., Methods: Forty-two patients having cataract surgery were randomly divided into 3 groups the day before surgery. The first group received 2 oral 500 mg doses of ciprofloxacin at 12-hour intervals. The second group received a single oral 500 mg dose of levofloxacin. The third group received a single oral 400 mg dose of moxifloxacin. At the time of surgery, 0.1 mL aqueous fluid was aspirated from the anterior chamber just before the operation and immediately stored at -80 degrees C. Drug concentrations were measured using a biological assay., Results: The mean aqueous level of ciprofloxacin was 0.50 microg/mL +/- 0.25 (SD); of levofloxacin, 1.50 +/- 0.50 microg/mL; and of moxifloxacin, 2.33 +/- 0.85 microg/mL. The mean aqueous levels of levofloxacin and moxifloxacin were above the 90% minimum inhibitory concentration for most of the common microorganisms that cause endophthalmitis., Conclusions: Therapeutic concentrations of fluoroquinolones, mainly levofloxacin and moxifloxacin, were reached with oral administration. These antibiotics may be effective for prophylaxis and adjuvant therapy of bacterial endophthalmitis.

Objective: To determine concentrations of ofloxacin and ciprofloxacin hydrochloride in aqueous humor after topical or combined topical and oral administration in eyes with filtering blebs., Design: A prospective, investigator-masked, randomized, controlled comparative study involving 36 eyes of 34 patients with functioning filtering blebs who were to undergo cataract surgery. Treatment groups received either topical ofloxacin or topical ciprofloxacin (instillation of 0.3% ophthalmic solution every 30 minutes for 4 hours before surgery), or a combined topical plus oral regimen (ciprofloxacin hydrochloride, four 100-mg tablets, or ofloxacin, one 400-mg tablet, administered 24-26, 12-14, and 2 hours preceding surgery). The main outcome measure was antibiotic concentration measured by chromatographic separation and mass spectrometry of aqueous samples obtained during surgery., Results: Topical antibiotic treatment yielded mean concentrations of ofloxacin, 0.75 microg/mL, and ciprofloxacin, 0.21 microg/mL, in aqueous. With combined topical and oral therapy, significantly more ofloxacin was measured than ciprofloxacin (3.84 microg/mL vs 0.35 microg/mL [P<.001]). The combination regimen produced significantly greater ofloxacin levels than did topical therapy alone (P =.007)., Conclusions: Ofloxacin penetrates better than ciprofloxacin into the aqueous of eyes with filtering blebs, particularly after combined topical and oral administration, by which ofloxacin reaches more than a 10-fold greater concentration than does ciprofloxacin. Combined topical and oral therapy with ofloxacin may be beneficial in the treatment of bleb-associated infections.

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.

A previous study of the present authors on gel-forming erodible inserts, based on high molecular weight (MW, 400 kDa) poly(ethylene oxide) (PEO), for ocular controlled delivery of ofloxacin (OFX) has been extended to investigate the effects of PEO MW, in the 200-2000 kDa range, on insert properties relevant to therapeutic efficacy. Mucoadhesion has shown a dependence on MW, with a maximum for PEO 400. The in vitro drug release from inserts based on PEO 200, PEO 400 and PEO 900 was mainly controlled by insert erosion, whereas with PEO 2000 it was mainly diffusion-controlled in a first phase, followed by an erosion-controlled phase. The erosion time scale depended directly on MW. Immediately after application in the lower conjunctival sac of the rabbit eye, the inserts based on PEO of whichever MW formed mucoadhesive gels, well tolerated by the animals; then the gels spread over the corneal surface and eroded. PEO 2000 was unsuitable as an insert material, since the resulting gel spilled from the eye, due to excessive swelling. The gel residence time in the precorneal area, the drug permanence time in the aqueous humor at concentrations > MIC and the time to reach the maximal drug concentration in the aqueous humor (C(max)) depended directly on MW, indicating that transcorneal absorption was governed by gel erosion. All inserts increased Cmax and AUCeff (AUC for concentrations > MIC) with respect to the commercial eyedrops. The increases caused by PEO 400 and PEO 900 were similar (3.78- and 3.16-fold, respectively, for Cmax; 11.06- and 12.37-fold, respectively, for AUCeff), whereas smaller increases were produced by PEO 200. The PEO 400 and PEO 900 inserts have shown a potential for a topical treatment of endophthalmitis.

This report describes the efficacy of a novel mucoadhesive polymer, the tamarind seed polysaccharide, as a delivery system for the ocular administration of hydrophilic and hydrophobic antibiotics. Healthy rabbits were subjected to repeated ocular instillations with either conventional gentamicin or ofloxacin or these agents viscosified with the tamarind seed polysaccharide. Administration of viscosified preparations produced antibiotic concentrations both in the aqueous humour and cornea that were significantly higher than those achieved with the drugs alone. The increased drug absorption and the prolonged drug elimination phase obtained with the viscosified formulations indicate the usefulness of the tamarind seed polysaccharide as an ophthalmic delivery system for topical administration of antibiotics.

Purpose: This study aimed to investigate the penetration of topical and oral ofloxacin into aqueous humor and vitreous humor in post-traumatic endophthalmitis model in rabbits., Methods: A standardized intraocular infection after penetrating injury was made in the right eyes of 16 rabbits. Intraocular infection was induced by intravitreal injection of a suspension of Staphylococcus aureus. The intact left eyes were maintained as controls. The animals were divided randomly into two groups. (1) In the topical group, two drops of ofloxacin 0.3% eyedrops were instilled to both eyes every 30 min for 4 h. (2) In the topical-oral group, two doses of 25 mg/kg of ofloxacin at 12-h intervals were given orally, then the protocol of the first group was applied. Aqueous and vitreous humor samples were taken 30 min after the last drop. Ofloxacin concentrations were measured by using HPLC., Results: Mean aqueous levels of ofloxacin in control eyes were: 3.25 +/- 2.55 microg/ml in topical group. 4.58 +/- 5.39 microg/ml in topical-oral group. Mean aqueous levels in inflamed eyes were: 5.21 +/- 4.55 microg/ml in topical group, 10.34 +/- 8.88 microg/ml in topical-oral group. Mean vitreous levels of ofloxacin in control eyes were: 0.17 +/- 0.07 microg/ml in topical group, 1.30 +/- 1.23 microg/ml in topical-oral group. Mean vitreous levels in inflamed eyes were: 0.35 +/- 0.22 microg/ml in topical group, 3.48 +/- 2.69 microg/ml in topical-oral group. There was no significant difference among the groups (P > 0.05), however., Conclusions: The result of this study suggests that oral supplementation of ofloxacin to topical instillation increased the ocular levels of ofloxacin in the post-traumatic endophthalmitis model. Mean drug concentrations in aqueous and vitreous humors were above the 90% minimum inhibitory concentrations (MIC90) for most of the common microorganisms causing endophthalmitis in all eyes, except in the vitreous humors of the intact eyes instilled topically.

Objective: To investigate the penetration of levofloxacin, an optical S-(-)isomer of ofloxacin, into the aqueous and vitreous humor after oral administration., Design: Randomized, clinical trial comparing tissue levels of levofloxacin after one or two doses 12 hours apart., Participants: Forty-five patients undergoing initial vitrectomy between February 1997 and June 1997 at the UIC Eye Center., Methods: Aqueous, vitreous, and serum samples were obtained and later analyzed from 45 patients after oral administration of 1 500-mg tablet (group 1, 22 patients) or 2 500-mg tablets (group 2, 23 patients) 12 hours apart before surgery., Main Outcome Measures: Aqueous, vitreous, and serum concentrations of levofloxacin (micrograms/milliliter)., Results: Group 1 achieved mean aqueous, vitreous, and serum levels of 0.59 +/- 0.48 microg/ml, 0.32 +/- 0.34 microg/ml, and 4.34 +/- 3.59 microg/ml, respectively. Group 2 achieved mean aqueous, vitreous, and serum levels of 1.90 +/- 0.97 microg/ml, 2.39 +/- 0.70 microg/ml, and 8.02 +/- 3.14 microg/ml., Conclusions: Mean inhibitory aqueous and vitreous MIC90 levels were achieved against a majority of ocular pathogens, including Staphylococcus aureus and Staphylococcus epidermidis, Streptococcus pneumoniae (vitreous), Bacillus cereus (vitreous), Haemophilus influenzae, Moraxella catarrhalis, and most gram-negative aerobic organisms except Pseudomonas aeruginosa after two doses given 12 hours apart. Mean MIC90 levels were obtained in the vitreous for a majority of pathogens responsible for traumatic, postoperative, or bleb-related endophthalmitis.

Purpose: To evaluate aqueous humour levels of topical 0.3% ciprofloxacin and 0.3% ofloxacin in the same subjects., Methods: Thirty-two bilateral cataractous patients received topical 0.3% ciprofloxacin in one eye and 0.3% ofloxacin in the other eye before each cataract extraction. Eyedrops were repetitively instilled for 6 h. Aqueous humour samples were collected and assayed for drug concentrations by a method described originally by us using high-performance liquid chromatography., Results: Mean aqueous ciprofloxacin and ofloxacin levels were 0.33 +/- 0.04 microgram/ml (mean +/- SEM) and 1.34 +/- 0.14 micrograms/ml respectively (p < 0.0001)., Conclusion: Ofloxacin level in the aqueous humour is 4 times higher than that of ciprofloxacin in the same subjects.

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.

Background: A prospective study was undertaken to determine the transcorneal penetration of three topically applied fluoroquinolones into aqueous humor., Methods: Cataract patients (n = 224) preoperatively received topically applied gyrase inhibitors (0.3% ciprofloxacin, 0.3% norfloxacin, 0.3% ofloxacin) in two different application modes. In application mode I, patients received on the day before operation 3 x 1 eye drop at 2-h intervals, and on the day of operation 3 drops at 1-h intervals. In application mode II, patients received 9 drops at 15-min intervals on the day of operation only. Just before cataract surgery 50-100 ml aqueous humor was aspirated and stored at -80 degrees C. The HPLC method was used for measuring the concentration., Results: The highest concentrations of all tested antibiotics were measured after the mode of application in which one drop was given every 15 min between 06:00 and 08:00 hours before operation. In this mode, ciprofloxacin achieved a mean aqueous level of 379.8 +/- 327.8 mg/l (range 33-1388 mg/l), norfloxacin 182.1 +/- 118.1 mg/l (range 38-480 mg/l) and ofloxacin 563.9 +/- 372.1 mg/l (range 64-1455 mg/l). These mean concentration are all above the MIC90 of gram-negative bacteria like Proteus mirabilis and Escherichia coli. In some cases the concentrations of ciprofloxacin and ofloxacin, but never norfloxacin, reached therapeutic values above the MIC90 of Staphylococcus aureus and Staphylococcus epidermidis., Conclusions: The mean concentration value of 0.3% ciprofloxacin and of 0.3% ofloxacin in the aqueous humor reached the MIC90 values of the frequently occurring gram-positive and gram-negative bacteria. Of the currently available topical fluoroquinolones, ofloxacin achieved the highest aqueous humor concentration. Considering the higher antimicrobial activity of ciprofloxacin, both ciprofloxacin and ofloxacin may be useful ophthalmic agents in antibacterial management, but they are not efficient against Streptococcus pneumoniae and Pseudomonas aeruginosa.

This study was designed to measure the concentration of ofloxacin in aqueous humor after topical, oral and intravenous administration in 50 patients undergoing cataract extraction. In Group 1, ofloxacin 0.3% eyedrops were topically instilled ten times and the aqueous humor concentration was 2.73 +/- 0.88 microg/ml. In Group 2, ofloxacin 0.3% eyedrops were topically instilled six times and the aqueous humor concentration was 0.84 +/- 0.61 microg/ml. Aqueous humor concentration 12 hours after 200 mg oral dose in Group 3, was 0.38 +/- 0.12 microg/ml. In Group 4, patients were given ofloxacin as a single intravenous 200 mg dose and the aqueous humor concentration 2 hours after the end of infusion was 0.45 +/- 0.11 microg/ml. Concentrations were determined by high performance liquid chromatography (HPLC) with fluorescence detection. There was a significant difference between Group 1 and the other groups, but not between Group 2 and Groups 3, 4. It was concluded that ofloxacin penetrates the corneal and the blood-aqueous barriers and can achieve good aqueous levels when given topically and systematically. Ofloxacin can be applied topically for external bacterial infections such as conjunctivitis and keratitis. Systematically administered ofloxacin reached higher levels than the MIC for some bacteria which cause endophthalmitis.

Purpose: To determine aqueous and vitreous humor ofloxacin levels following oral and topical application of ofloxacin in patients with noninflamed cornea and intact crystalline lens, and to compare the drug levels provided by each route., Materials and Methods: Twenty-six patients undergoing pars plana vitrectomy for various ocular pathologies were divided into two groups. Fourteen patients received two drops of 0.3% ophthalmic solution of ofloxacin every 30 minutes for 3 hours and every 60 minutes for the next 3 hours, and 12 patients received a single oral dose of 400 mg ofloxacin 8 hours before surgery. The aqueous and vitreous humor samples were simultaneously collected after oral or topical administration during pars plana vitrectomy to assess penetration of the drug. Samples were assayed for ofloxacin concentrations by a previously described method using high-performance liquid chromatography., Results: The aqueous and vitreous humor levels of ofloxacin were 1.54 +/- 0.27 microg/mL (mean +/- standard error) and 1.77 +/- 0.24 microg/mL after oral and 1.44 +/- 0.24 microg/mL and 0.37 +/- 0.05 microg/mL after topical ofloxacin administration, respectively. Aqueous humor levels were not statistically different following oral or topical administration (P > 0.8). However, vitreous level of the drug after oral administration was significantly higher than that after topical administration (P < 0.001)., Conclusion: Ocular bioavailability of ofloxacin in aqueous humor after oral and topical administration is similar when the drug is applied as described. Penetration of ofloxacin into vitreous humor is less than that into aqueous humor following topical application. The aqueous humor levels of ofloxacin via both routes and the vitreous level of the drug after oral route exceed the minimum inhibitory concentrations for certain bacterial species that frequently cause intraocular infection.

Unlabelled: The purpose of this study was to determine the aqueous humor concentrations of topically applied ciprofloxacin (CAS 86393-32-0), ofloxacin (CAS 82419-36-1) and tobramycin (CAS 79645-27-5). Thirty patients undergoing cataract extraction or trabeculectomy were randomly divided into three groups and each of the group received either 0.3% ciprofloxacin, ofloxacin or tobramycin topical drops preoperatively. Eyedrops were instilled for six times at a frequency of one drop every 15 minutes, beginning 90 minutes before initiation of the surgery. At the time of surgery, 0.1 ml aqueous fluid was aspirated from the anterior chamber. Concentrations of the antimicrobial agents were determined using the microbroth dilution procedure outlined by the National Committee for Clinical Laboratory Standards. Escherichia coli (ATCC 25922) was used as a standard strain for determination of minimal inhibitory concentrations (MICs). The mean aqueous levels of ciprofloxacin and ofloxacin were found to be 0.092 +/- 0.077 microgram/ml, 0.964 +/- 0.693 microgram/ml, respectively. Tobramycin did not reach the concentration that could be detected by applied method., Conclusion: The mean aqueous humor levels of ofloxacin and ciprofloxacin were more than the MICs levels for most of the ocular pathogens which may cause postoperative endophthalmitis.

Objectives: To investigate the intracorneal, aqueous, and vitreous penetration of ofloxacin, and to assess the concentration of the drug after topical administration alone and after combined topical and oral administration., Methods: Twenty consecutive patients undergoing penetrating keratoplasty with vitrectomy for bullous keratopathy received 2 drops of 0.3% ofloxacin every 30 minutes starting 4 hours before surgery. Group A (10 patients) received topical therapy alone. Group B (10 patients) received an additional 3 doses of oral ofloxacin, 400 mg, every 12 hours starting 26 hours before surgery. Aqueous humor, vitreous humor, and corneal specimens were analyzed for ofloxacin levels., Results: For group A, the mean intracorneal ofloxacin level was 4.51 micrograms/mL (range, 0.58-8.77 micrograms/mL; 10 specimens), the mean aqueous humor level was 1.34 micrograms/mL (range, 0.07-4.98 micrograms/mL; 8 specimens), and the mean vitreous humor level was 0.37 micrograms/mL (range, 0.05-0.90 micrograms/mL; 8 specimens). For group B, the mean intracorneal ofloxacin level was 8.59 micrograms/mL (range, 1.18-23.24 micrograms/mL; 10 specimens), the mean aqueous humor level was 2.77 micrograms/mL (range, 0.25-5.80 micrograms/mL; 10 specimens), and the mean vitreous humor level was 2.55 micrograms/mL (range, 0.28-4.97 micrograms/mL; 9 specimens)., Conclusions: Topically applied ofloxacin achieves therapeutic levels in the cornea and aqueous. Mean levels achievable are well above the 90% minimal inhibitory concentration (MIC90) for the majority of bacteria responsible for endophthalmitis and corneal ulceration. The addition of oral ofloxacin to topical therapy increased vitreous penetration 7-fold in this assay trial.

It is well known that some ocular diseases can be treated more effectively with a collagen shield containing drug. The influence of collagen cross-linking on drug delivery is not known. We determined if collagen cross-linking affects ofloxacin bioavailability at three different collagen shield dissolution times. In this study, the collagen shields were not impregnated in drug but an eye drop was simply instilled after application of collagen shield. A non-cross-linked collagen shield, with a dissolution time of 12 h, disappeared more rapidly from the rabbits' eyes due to proteolysis after application in vivo. On the other hand, the cross-linked collagen shields, with dissolution times of 24 and 72 h, served as an ofloxacin depot and enhanced topical ofloxacin penetration into the cornea and the aqueous humor. As the dissolution times for the cross-linked collagen shield are longer than those of the non-cross-linked type, they serve as drug reservoirs. Therefore, cross-linked collagen shields might be useful ocular drug delivery devices because they can allow drug concentrations to achieve higher levels in the cornea and aqueous humor.

Objective: A prospective study was undertaken to determine the transcorneal penetration of three topically applied fluoroquinolones into aqueous humour., Methods: Two hundred and twenty-four patients undergoing cataract extraction received 0.3% ciprofloxacin, norfloxacin or ofloxacin eye drops by two different administration modes with different frequencies and intervals of application. At the beginning of cataract extraction (0.5-3 h after the last drop), 50-100 microliters aqueous fluid was aspirated from the anterior chamber and immediately stored at -80 degrees C. Antibiotic concentrations were measured using high-performance liquid chromatography., Results: Generally, topical ofloxacin and ciprofloxacin yielded aqueous humour levels higher than topical norfloxacin. The highest concentrations of all tested fluoroquinolones were measured after using an application mode, in which one drop was given every 15 min between 0600 hours and 0800 hours, prior to operation. When applied by this mode, ciprofloxacin achieved a mean aqueous level of 0.380 (+/- 0.328) microgram.ml-1 (range 0.033-1.388 micrograms.ml-1), norfloxacin 0.182 (0.118) microgram.ml-1 (range 0.038-0.480 microgram.ml-1) and ofloxacin 0.564 (0.372) microgram.ml-1 (range 0.064-1.455 micrograms.ml-1). These mean concentrations were above the minimum inhibitory concentration (MIC90), concentrations required for inhibition of 90% of pathogen strains in vitro of gram-negative bacteria, such as Proteus mirabilis and Escherichia coli. Therapeutic values above the MIC90 of Staphylococcus epidermidis, the pathogen causing eye infections most frequently, were reached by 67.5% of patients after ofloxacin and by 41% after ciprofloxacin, but never after norfloxacin treatment., Conclusion: Of the currently available topical fluoroquinolones, ofloxacin achieved the highest aqueous humour concentration. This fluoroquinolone may be an useful ophthalmic agent for topical antibacterial management, but it does not seem to be prophylactically effective against Streptococcus pneumoniae or Pseudomanas aeruginosa.

Purpose: To determine the aqueous and vitreous fluid penetration of ofloxacin after a combined topical and single intravenous dose protocol before vitrectomy surgery., Materials and Methods: Before undergoing vitrectomy surgery, patients were given two drops of ofloxacin 0.3% topically and a single intravenous dose of ofloxacin 400 mg. Aqueous (mean, 43 minutes) and vitreous (mean, 53 minutes) fluid samples were collected at the start of the surgical procedure. The samples were analyzed for ofloxacin penetration., Results: The mean aqueous fluid concentration was 1.083 micrograms/mL +/- 0.406. The mean +/- SD vitreous fluid concentration in nondiabetic patients with intact vitreous was 0.352 microgram/mL +/- 0.301. Vitreous levels obtained more than 50 minutes after administration (0.414 microgram/mL +/- 0.336) were generally higher than those obtained after less than 50 minutes (P = 0.12). Eyes with prior vitrectomies achieved better ofloxacin penetration (0.984 microgram/mL +/- 0.680) than did nonvitrectomized eyes., Conclusion: Ofloxacin achieved measurable aqueous fluid penetration after topical and intravenous administration. Aqueous levels were above the minimum inhibitory concentration for most ocular pathogens. Vitreous levels were adequate in vitrectomized eyes to achieve inhibitory concentrations against many common ocular pathogens. Combined preoperative topical and a single dose of intravenous ofloxacin may provide inhibitory aqueous and vitreous antibiotic levels in vitrectomized eyes in cases where intravitreal antibiotics are not considered and oral administration is not practical.

Ofloxacin 0.3% ophthalmic solution or ointment was administered preoperatively to 13 patients undergoing cataract surgery. Mean drug concentrations in conjunctival biopsies were 2.62 and 6.55 micrograms/gm and in aqueous humor samples were 0.36 micrograms/mL and 0.43 micrograms/mL, for ointment and solution respectively. Mean conjunctival concentrations of ofloxacin achieved MIC90 values for 419 gram-positive and gram-negative organisms previously analyzed.

Objective: To compare the efficacy of two treatment regimens, tobramycin drops-erythromycin ointment and ofloxacin drops-placebo ointment, in sterilizing the external ocular adnexa when given perioperatively. A second objective was to determine the aqueous humour concentration of ofloxacin and tobramycin., Design: Randomized double-blinded clinical trial., Setting: University-affiliated hospital., Patients: Patients aged 18 years or more scheduled to undergo planned cataract surgery who were judged likely to complete the trial., Numbers: Of 55 patients enrolled 6 were disqualified and 49 completed the trial., Interventions: Preoperative instillation of 10 drops of a 0.3% solution of ofloxacin (26 eyes) or tobramycin (23 eyes) in the operative eye, starting the evening before surgery. Tobramycin-treated eyes received erythromycin ointment after surgery; ofloxacin-treated eyes received petrolatum ointment. Lid and conjunctival swabs were obtained from both eyes on the day before surgery (visit 1), at surgery (visit 2) and on the first postoperative day (visit 3). Aqueous humour samples were obtained from the study eyes at surgery., Main Outcome Measures: Threshold growth of bacteria on culture, aqueous humour concentration of ofloxacin or tobramycin., Results: At visit 1, 96% of all eyes had positive cultures; this result persisted at visits 2 and 3 for the control eyes. For the treated eyes the incidence of positive cultures decreased from visit to visit. By visit 3 lid cultures were positive for 7 (27%) of the ofloxacin-treated eyes and 7 (30%) of the tobramycin-treated eyes; conjunctival cultures were positive for 0 (0%) of the ofloxacin-treated eyes and 1 (4%) of the tobramycin-treated eyes. No significant differences were seen in culture positivity between the treatment groups at any visit. The mean aqueous humour concentration of ofloxacin was significantly higher than that of tobramycin (0.4084 vs. 0.0279 microgram/mL) (p < 0.001)., Conclusions: Both ofloxacin-placebo treatment and tobramycin-erythromycin treatment were more effective than no treatment in sterilizing the external ocular adnexa. The two treatments were equally efficacious in eliminating bacteria, more successfully in the conjunctiva than the lids. Topically administered ofloxacin demonstrated significantly greater anterior chamber penetration than topically administered tobramycin.

Purpose: To determine the intraocular penetration of topically applied fluoroquinolone antibiotics into aqueous humor., Methods: Thirty-two patients undergoing cataract extraction received either 0.3% ciprofloxacin, 0.3% norfloxacin, or 0.3% ofloxacin topical drops. The patients were given two drops 90 minutes preoperatively and two drops 30 minutes preoperatively. At the time of surgery, 0.1 ml aqueous fluid was aspirated from the anterior chamber and immediately stored at -70 degrees C., Results: Concentrations of ciprofloxacin, norfloxacin, and ofloxacin were determined using a broth dilution bioassay. Morganella morganii with a known minimal inhibitory concentration was used to assay ciprofloxacin and norfloxacin levels. Salmonella enteritidis with a known minimal inhibitory concentration was used to assay ofloxacin levels. Topically applied ciprofloxacin achieved a mean aqueous level of 0.072 microgram/ml (range, 0.02-0.153 microgram/ml). One sample was below the sensitivity of the bioassay. Topical norfloxacin achieved a mean aqueous level of 0.0570 microgram/ml (range, 0.046-0.10 microgram/ml). Seven samples did not reach the sensitivity of the bioassay. Topical ofloxacin achieved a mean level in the aqueous humor of 0.338 microgram/ml (range, 0.078-0.625 microgram/ml). There was no statistically significant difference in intraocular aqueous humor levels of ciprofloxacin versus norfloxacin (P > 0.05). Topical ofloxacin achieved aqueous humor levels significantly higher than either ciprofloxacin or norfloxacin (P < 0.004)., Conclusion: Of the currently available topical fluoroquinolone antibiotics, ofloxacin achieves the highest aqueous humor concentrations.

We studied the aqueous humor penetration of ofloxacin after topical, oral, and intravenous administration in 51 consecutive patients undergoing cataract surgery. Aqueous humor concentration (mean +/- SD) was 0.53 +/- 0.35 mg/l when ofloxacin 0.3% eyedrops were instilled topically six times, one drop every three hours, until 90 minutes preoperatively, and 0.63 +/- 0.29 mg/l (P = .45) when two additional instillations were made, one drop every 30 minutes, until 30 minutes before aqueous humor aspiration. Aqueous humor concentration two hours after a single 200-mg oral dose (0.38 +/- 0.15 mg/l) was significantly lower (P = .048) than that 12 hours after the same oral dose (0.58 +/- 0.24 mg/l). Two hours following an intravenous infusion of 200 mg of ofloxacin, aqueous humor concentration was 0.33 +/- 0.19 mg/l. Our results suggest that therapeutic levels above the minimum inhibitory concentration for many bacteria cultured in endophthalmitis can be achieved in aqueous humor after either topical or oral administration, which indicates that this antibiotic passes easily through the corneal and the blood aqueous barriers.

Eighty-five patients undergoing cataract surgery were given for prophylaxis of intraocular infection two intravenous doses each of 200 mg, 300 mg or 400 mg ciprofloxacin (35 patients), 400 mg or 800 mg pefloxacin (30 patients), or 400 mg ofloxacin (20 patients). Ciprofloxacin levels in aqueous humour ranged from 0.02 to 0.50 microgram/ml, pefloxacin levels from 1.04 to 7.80 micrograms/ml, and ofloxacin levels from 0.44 to 2.27 micrograms/ml with ratios of aqueous humour to serum levels ranging from 3.8% to 25%, 21% to 48.1% and 44% to 88.4%, respectively. It is concluded that the quinolones studied might be suitable for surgical prophylaxis or treatment of anterior chamber infections due to Enterobacteriaceae, while ciprofloxacin at high doses is preferable for Pseudomonas aeruginosa infections.

Tear and aqueous humor levels of ofloxacin following 40mg of topical 0.3% ointment were determined at intervals within 24 hours by high performance liquid chromatography. The highest tear level was detected in half an hour, and effective concentrations existed in 6 hours. The highest aqueous humor level was detected 60 minutes after administration. Ofloxacin ointment produced higher tear concentrations for longer time than did aqueous solution of the drug.