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

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

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

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

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

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

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

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

Human aqueous humor levels of oral ciprofloxacin, levofloxacin, and moxifloxacin

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.     

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

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

Aqueous penetration of gatifloxacin and levofloxacin into the rabbit aqueous humor following topical dosing.

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.     

An in vivo study comparing the ocular absorption of levofloxacin and ciprofloxacin prior to phacoemulsification

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.     

Ocular bioavailability of ciprofloxacin in sustained release formulations.

A novel sustained release delivery system of ciprofloxacin for the eye was developed. The system consists of a viscosity enhancer (carbopol gel or hydroxypropylmethylcellulose solution) plus a penetration enhancer (dodecylmaltoside) to overcome penetration barriers and loss due to wash-out and thus achieve the desired ciprofloxacin ocular absorption. The present studies were designed to assess the ocular penetration and bioavailability of ciprofloxacin in sustained release formulations. In vitro studies in rabbits indicated an approximate 10-fold increase in drug penetration through the rabbit cornea using the penetration enhancer, dodecylmaltoside. In vivo bioavailability studies demonstrate that these formulations provided a long drug duration in the cornea. After administration of a single topical dose of ciprofloxacin (0.3%/30 microL), corneal levels greater than the Minimum Inhibitory Concentration (MIC90) (0.5 microg/g) were observed through eight hours. These sustained release formulations delivered 10-fold more drug into the aqueous humor than the standard solution formulation. Maximum ciprofloxacin concentrations in the aqueous humor (0.5-0.7 microg/mL) were attained between one and two hours after dosing. Using these sustained release formulations, ciprofloxacin can penetrate to the anterior chamber of the eye in concentrations that are inhibitory for most gram-negative and gram-positive organisms. These topical ocular formulations have prophylactic utility for prevention of post-surgical infection, offering greater efficacy and safety than currently available treatments.     

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

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

Aqueous humor levels of topically applied levofloxacin in human eyes

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

Topical 0.3% ciprofloxacin, norfloxacin, and ofloxacin in treatment of bacterial keratitis: a new method for comparative evaluation of ocular drug penetration.

AIMS--This study was designed to assess the relative corneal penetration of topical drops of three antibiotics and to relate those levels to minimum inhibitory concentrations for organisms associated with bacterial keratitis. METHODS--Four drops of each of ciprofloxacin, norfloxacin, and ofloxacin (0.3% topical ophthalmic preparations) were given to 12 patients undergoing corneal transplantation. After the recipient tissue was removed, corneal drug penetration was measured using high performance liquid chromatography. RESULTS--Intracorneal concentrations of ofloxacin (geometric mean 0.81 mg kg-1) were significantly higher than both ciprofloxacin (0.60 mg kg-1; p = 0.048) and norfloxacin (0.54 mg kg-1; p = 0.012). Ciprofloxacin and norfloxacin concentrations did not differ significantly (p = 0.33). CONCLUSIONS--Review of the minimum inhibitory concentrations of the fluoroquinolones against ocular pathogens reveals that ciprofloxacin is more potent than ofloxacin against many bacteria; ofloxacin is in turn more potent than norfloxacin. These data favour the selection of ciprofloxacin and ofloxacin rather than norfloxacin for the empirical treatment of corneal infection. The greater potency of ciprofloxacin offsets the superior penetration of ofloxacin. There is a need for improved clinical trial data concerning the use of fluoroquinolone eyedrops in ulcerative keratitis; some encouraging data are available for ciprofloxacin but not (in humans) for norfloxacin or ofloxacin.     

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

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

Ocular pharmacokinetics of moxifloxacin after topical treatment of animals and humans

The ocular penetration and pharmacokinetics of moxifloxacin in comparison to other fluoroquinolones (ofloxacin, ciprofloxacin, gatifloxacin, norfloxacin, levofloxacin, and lomefloxacin) have been determined by in vitro and ex vivo techniques, as well as in animal and human studies. This article reviews the original pharmacokinetics work performed by Alcon and other studies reported in the ocular fluoroquinolone literature. The results consistently demonstrate higher maximum concentrations for moxifloxacin relative to the other fluoroquinolones in ocular tissues with levels well above its minimum inhibitory concentrations for relevant ocular pathogens. This superior performance is due to the unique structure of moxifloxacin that combines high lipophilicity for enhanced corneal penetration with high aqueous solubility at physiological pH. The latter property creates a high concentration gradient at the tear film/corneal epithelial interface providing a driving force for better ocular penetration for moxifloxacin. In addition, the higher concentration of moxifloxacin in VIGAMOX (i.e., 0.5% vs. 0.3%) allows more antibiotic to be available to ocular tissues. It is clear from the array of studies summarized in this report that moxifloxacin penetrates ocular tissues better (two- to three-fold) than gatifloxacin, ciprofloxacin, ofloxacin, or levofloxacin. This consistent, enhanced penetration of topical moxifloxacin offers powerful advantages for ophthalmic therapy.     

Aqueous and vitreous penetration of levofloxacin after topical and/or oral administration

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.     

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

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

Penetration of betaxolol HCL ionic suspension 0.25% and betaxolol HCL solution 0.50% into the aqueous humor

PURPOSE: To determine the intraocular penetration of topical drops of betaxolol HCl 0.25% suspension and betaxolol HCl 0.50% solution into the aqueous humor. METHODS: Fifteen patients were randomly assigned to receive topical betaxolol HCl 0.25% suspension (n=7) or topical betaxolol HCl 0.50% solution (n=8) the day before cataract surgery. Aqueous samples were collected 2 hours after the administration of the morning dose during cataract surgery. Drug concentrations were determined by high-performance liquid chromatography with fluorescence detection. RESULTS: The mean aqueous humor concentration of topical betaxolol HCl 0.25% suspension was 275.1+/-168.8 micro g/mL (range 570-70 micro g/mL) and the mean aqueous humor concentration of topical betaxolol HCl 0.50% solution was 195.4+/-102.4 micro g/mL (range 334-50 micro g/mL) (p=0.281). CONCLUSIONS: The mean aqueous humor concentration of betaxolol 0.25% suspension was higher than betaxolol 0.50% solution; however, the difference was not statistically significant. With twofold reduced concentration and similar anterior chamber penetration, betaxolol 0.25% suspension could be first choice for Beta 1 selective blocker therapy when considered for patients with glaucoma.     

Penetration of topical ciprofloxacin by presoaked medicated soft contact lenses.

PURPOSE: To assess the penetration of topical ciprofloxacin by a presoaked medicated disposable soft contact lens without topical drop administration. METHODS: Disposable soft contact lenses were presoaked in 0.3% topical ciprofloxacin (Ciloxan, Alcon Laboratories, Fort Worth,TX) for 10-12 hours. Presoaked lenses were placed on the eyes of patients with senile cataracts for 3 hours in group A, 5-6 hours in group B, and 8-12 hours in group C prior to their scheduled lens extraction surgery. Aqueous humor samples were drawn by paracentesis during the operation. Ciprofloxacin concentrations were determined by high pressure liquid chromatography-fluorescence detection. RESULTS: The mean ciprofloxacin concentration was 2.70 +/- 0.98 microg/mL in group A, 1.22 +/- 1.0 microg/mL in group B, and 0.5 +/- 0.2 microg/mL in group C. CONCLUSIONS: Penetration of topical ciprofloxacin is enhanced through a presoaked disposable soft contact lens, and at 3 hours therapeutic levels are obtained. Significant levels of ciprofloxacin are retained through 8-12 hours. This mode of treatment may increase patient compliance compared to frequent topical drop administration, and as a consequence, assure efficient treatment of keratitis, at least for the first 3 hours.     

Penetration of gatifloxacin eye drops into the aqueous humor in humans

The authors topically administered gatifloxacin (GFLX) into the eye before cataract surgery and measured the concentrations of this agent to determine its penetration into aqueous humor. Seventy-seven patients with age-related cataracts who underwent cataract surgery were enrolled in this study. They received 0.3% GFLX ophthalmic solution 4 times at 30-min intervals, beginning 2 h before surgery. Aqueous humor was aspirated from the anterior chamber and assayed for GFLX concentration using high-performance liquid chromatography. The mean intraoperative GFLX concentration in aqueous humor was 0.485 +/- 0.328 microg/mL. GFLX level was 0.573 +/- 0.367 microg/mL in elderly patients, at least 70 years of age, and was significantly higher than that (0.322 +/- 0.135 microg/mL) in the patients less than 70 years old. This concentration was close to or higher than the minimum inhibitory concentrations required to inhibit the growth of 90% of major pathogens of endophthalmitis (MIC90), such as Staphylococcus aureus, Streptococcus pneumoniae, and Enterococcus faecalis associated with poor prognosis, other than Staphylococcus epidermidis, Pseudomonas aeruginosa, and MRSA (methicillin-resistant S. aureus) in vitro. The GFLX concentrations found in aqueous humor samples were sufficient to kill bacteria other than S. epidermidis, P. aeruginosa, and MRSA in vitro.     

人眼滴用氧氟沙星和环丙沙星及妥布霉素的前房穿透性研究

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