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.     

A double-masked three-month comparison between 0.25% betaxolol suspension and 0.5% betaxolol ophthalmic solution

In 352 patients with primary open-angle glaucoma or ocular hypertension, a multicenter double-masked, parallel-group clinical study compared the effects on intraocular pressure and ocular comfort of 0.5% betaxolol ophthalmic solution, a cardioselective beta-adrenergic blocking agent, with 0.25% betaxolol suspension. With twice-daily dosages, baseline intraocular pressure was significantly reduced (P = .0005), with no significant difference between the two groups, at Week 2 and at Months 1, 2, and 3. Further, the prevalence of ocular discomfort upon topical instillation was significantly lower for 0.25% betaxolol suspension than for 0.5% betaxolol solution (P = .0005).     

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.     

Concentrations of betaxolol in ocular tissues of patients with glaucoma and normal monkeys after 1 month of topical ocular administration

PURPOSE: To measure the concentration of betaxolol in tissues of humans with glaucoma and normal monkeys after topical administration. METHODS: Enucleated eyes (n = 7) of patients with glaucoma (age range, 27-79 years), without apparent anatomic disruption that would be likely to influence betaxolol absorption and intraocular distribution (exceptions: one pseudophakic, one aphakic) or other disease, were analyzed for betaxolol concentrations after self-administration of 0.25% betaxolol twice daily for 28 days or longer. The last instillation was made within 6 hours of surgery. Cynomolgus monkeys (n = 3) received 0.25% betaxolol twice daily unilaterally for 30 days. Betaxolol was measured by HPLC and tandem mass spectrometry (MS/MS) in plasma and ocular tissues. RESULTS: In humans, mean betaxolol concentrations (excluding the aphakic patient) were 71.4 +/- 41.8 ng/g in the retina, 31.2 +/- 14.8 ng/g in the optic nerve head, and 1290 +/- 1170 ng/g in the choroid. Mean concentrations in the iris and ciliary body were 73,200 +/- 89,600 and 4,250 +/- 3,020 ng/g, respectively. Betaxolol concentration was higher in all ocular tissues than in the plasma (0.59 +/- 0.32 ng/mL). In the monkeys the concentrations in the posterior tissues of the treated eyes were higher than in the untreated eyes, with mean differences in the retina and optic nerve head of 121 and 130 ng/g, respectively. CONCLUSIONS: Topically applied betaxolol was bioavailable to posterior ocular tissues, including the retina and optic nerve head, of patients with glaucoma and of normal cynomolgus monkeys. The higher betaxolol levels in the treated versus untreated monkey eyes are consistent with betaxolol's reaching posterior tissues by local absorption and distribution.     

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.     

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.     

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.     

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

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

Aqueous humor penetration of gatifloxacin and moxifloxacin eyedrops given in different concentrations in a wick before cataract surgery

PURPOSE: To determine whether the penetration into the aqueous humor of gatifloxacin (Zymar) and moxifloxacin (Vigamox) eyedrops was affected by altering their concentrations in the dilating mixture in which the wick used to dilate the pupil before cataract surgery was soaked. SETTING: Pasqua Hospital, Regina, Saskatchewan, Canada. METHODS: This prospective randomized open-label study comprised 65 women and 35 men who were divided into 2 main groups. One group received 1 mL of the antibiotic in the dilating mixture and the other, 2 mL. Each group was divided into 2 subgroups, 1 for gatifloxacin and 1 for moxifloxacin. At the beginning of surgery, 0.1 mL of aqueous humor was aspirated, frozen, and couriered to the provincial laboratory for analysis by high-performance liquid chromatography. RESULTS: In the first group, the mean concentration of gatifloxacin in the aqueous humor was 0.30 microg/mL +/- 0.21 (SD) and of moxifloxacin, 0.97 +/- 0.63 microg/mL. When the volume of the antibiotic in the dilating mixture was doubled, the mean concentration increased to 0.34 +/- 0.25 microg/mL and 1.37 +/- 0.79 microg/mL, respectively. Only the increased penetration of moxifloxacin was statistically significant. CONCLUSIONS: Moxifloxacin penetrated the aqueous humor better than gatifloxacin when given in a wick soaked in the dilating mixture before cataract surgery. Only the penetration of moxifloxacin increased significantly when the volume of the antibiotic in the dilating mixture was doubled. In both groups, only moxifloxacin reached and exceeded the minimum inhibitory concentration levels for the most common ocular pathogens causing endophthalmitis.     

Intraocular penetration of topical lidocaine 4%.

PURPOSE: To evaluate the intraocular penetration of lidocaine 4% topically applied before phacoemulsification. SETTINGS: Institute of Ophthalmology, University of Verona, and Department of Medical Pharmacology, University of Padua, Italy. METHODS: Thirty eyes having phacoemulsification for senile cataract were anesthetized by topical application of lidocaine 4%. The drug was applied 3 times in 30 minutes in 15 eyes and 6 times in 60 minutes in 15 eyes. At the beginning of surgery, aqueous humor samples were obtained to measure the lidocaine levels. Blood samples were obtained in 6 patients 30 and 60 minutes after aqueous humor collection. The aqueous humor levels were compared with the amount of pain perceived by patients during surgery. RESULTS: Mean aqueous humor lidocaine concentration was 8.68 micrograms/mL +/- 2.43 (SD) after 3 instillations and 23.21 +/- 8.87 micrograms/mL after 6 instillations. Blood levels of lidocaine were negligible. Patients whose intraocular level was below 12 micrograms/mL perceived more pain during surgery. Only 2 eyes had these low levels after 6 instillations. CONCLUSIONS: Topically applied lidocaine 4% effectively penetrates the eye, providing analgesia for phacoemulsification. We suggest at least 6 instillations in the hour preceding surgery. In this study, pain during surgery was primarily related to poor intraocular levels of the anesthetic agent.     

Effect of topical betaxolol on acute rise of aqueous flare induced by prostaglandin E(2) in pigmented rabbits.

PURPOSE: To evaluate the effects of topical betaxolol on experimental ocular inflammation. METHODS: Transcorneal diffusion of 25 microg/mL (7.09 x 10(-2) mmol/L) of prostaglandin E(2) (PGE(2)), placed in a glass cylinder, was employed to induce aqueous flare elevation in pigmented rabbits. Betaxolol was administered topically before PGE(2) application. Aqueous flare was measured with a laser flare cell meter. RESULTS: Four-, two-, and one-time topical instillations of betaxolol inhibited the PGE(2)-induced aqueous flare elevation by 44% +/- 8%, 32 +/- 7%, and 8 +/- 6%(mean +/- SD), respectively. The inhibition of flare elevation was dependent on the number of betaxolol instillations. CONCLUSION: Topical betaxolol has an inhibitory effect on PGE(2)-induced aqueous flare elevation in rabbit eyes.     

Comparison of ketorolac 0.4% and bromfenac 0.09% at trough dosing: aqueous drug absorption and prostaglandin E2 levels

PURPOSE: To compare aqueous drug concentrations and prostaglandin E(2) (PGE(2)) levels in patients treated with ketorolac 0.4% and bromfenac 0.09% at trough dosing. SETTING: Private practice, Wilkes-Barre, Pennsylvania, USA. METHODS: This single-center randomized investigator-masked clinical study comprised 56 patients having cataract surgery. Patients received 1 drop of ketorolac 0.4% or bromfenac 0.09% 6 hours and 12 hours preoperatively consistent with on-label dosing schedules. Aqueous humor was collected at the start of surgery and analyzed for concentrations of ketorolac and bromfenac using a reverse-phase high-performance liquid chromatography-mass spectroscopy system and for PGE(2) levels by competitive enzyme immunoassay. RESULTS: The mean aqueous PGE(2) level was 204.2 pg/mL +/- 95.5 (SD) in patients treated with ketorolac 0.4% and 263.7 +/- 90.0 pg/mL in patients treated with bromfenac 0.09%, (P = .020). The mean aqueous concentration of ketorolac and bromfenac at trough dosing was 130.5 +/- 37.8 ng/mL and 6.2 +/- 3.1 ng/mL, respectively (P = .004). CONCLUSIONS: Higher aqueous levels and greater PGE(2) inhibition were observed in cataract surgery patients treated with ketorolac 0.4% than in patients treated with bromfenac 0.09% at trough dosing. These findings suggest that ketorolac 0.4% administered 4 times a day may provide better control of prostaglandin-mediated inflammation than bromfenac 0.09% administered twice a day.     

Concentrations of levofloxacin, ofloxacin, and ciprofloxacin in human corneal stromal tissue and aqueous humor after topical administration

OBJECTIVE: To evaluate the penetration of commercially available levofloxacin 0.5%, ofloxacin 0.3%, and ciprofloxacin 0.3% topical ophthalmic solutions in human corneal stromal and aqueous humor tissues. METHODS: A total of 67 patients scheduled to undergo penetrating keratoplasty for treatment of stromal scar or dystrophy, keratoconus, pellucid marginal degeneration, or endothelial disease were enrolled in this prospective, double-blind, 3-center study. To be considered for inclusion, patients had to have an intact corneal epithelium and minimal or no corneal edema (pachymetry < 650 microm). After informed consent was obtained, patients were randomized to receive 1 drop of levofloxacin 0.5%, ofloxacin 0.3%, or ciprofloxacin 0.3% topical ophthalmic solution at approximately 15 and 10 minutes before surgery. Approximately 0.1 mL of aqueous fluid was aspirated by paracentesis through the trephination wound at the onset of surgery, followed by excision of the affected cornea and removal of its epithelium. Specimens were stored frozen at -70 degrees C until assayed by high-performance liquid chromatography. RESULTS: All 3 fluoroquinolones were well tolerated. A total of 65 corneas and 59 aqueous fluid samples were obtained and assayed. The mean +/- standard deviation corneal concentrations of ciprofloxacin, ofloxacin, and levofloxacin following a 2-drop administration were 9.92 +/- 10.99 microg/g (n = 18), 10.77 +/- 5.90 microg/g (n = 23), and 18.23 +/- 20.51 microg/g (n = 24), respectively. Although corneal stromal levels were highest in the levofloxacin group, the high degree of interpatient variability prevented demonstration of statistically significant differences when compared with ofloxacin (P = 0.377). In contrast, levofloxacin concentrations were approximately twice as high as ciprofloxacin, and this difference reached statistical significance (P = 0.014). The corresponding aqueous humor concentrations of ciprofloxacin, ofloxacin, and levofloxacin were 0.135 +/- 0.231 microg/mL (n = 15), 0.135 +/- 0.111 microg/mL (n = 20), and 0.372 +/- 0.546 microg/mL (n = 24, P < 0.001 versus ciprofloxacin and ofloxacin). CONCLUSION: The topical administration of all 3 agents was well tolerated in patients undergoing penetrating keratoplasty. Two drops of levofloxacin 0.5% solution results in a 1.7- to 2.7-fold greater penetration into human corneal stromal and aqueous humor tissues than ofloxacin 0.3% or ciprofloxacin 0.3%. The mean intracorneal concentrations of all three agents following 2 drops exceeds the MIC90 for the majority of pathogens causing bacterial keratitis. Topical levofloxacin appears to offer pharmacokinetic and pharmacodynamic advantages over ofloxacin and ciprofloxacin in terms of enhanced transcorneal penetration; however, clinical comparative trials are needed to confirm these relative advantages.     

Aqueous humor erythropoietin levels in patients with primary open-angle glaucoma

PURPOSE: To evaluate the levels of erythropoietin (EPO) in the aqueous humor in eyes with primary open-angle glaucoma (POAG) and without glaucoma. METHODS: Levels of EPO were measured using a sandwich enzyme-linked immunosorbent assay kit in aqueous humor aspirates taken during anterior segment surgery from 45 patients, of whom 20 had POAG and 25 had senile cataract only. RESULTS: The mean aqueous humor EPO concentration in eyes with POAG (10.91+/-4.32 mU/mL) was significantly higher than that from eyes with cataract (8.24+/-1.77 mU/mL, P=0.008). There was no significant difference between the serum EPO concentrations of POAG (26.46+/-10.36 mU/mL) and the control group (24.50+/-7.59 mU/mL, P=0.468). There was no correlation (P=0.165) between the EPO aqueous humor concentration and the EPO serum concentration while there was no correlation between the EPO aqueous humor concentration and the EPO serum concentration in the control group (P=0.819). CONCLUSIONS: The aqueous humor EPO level is increased in eyes with POAG.     

Ocular penetration of cefepime following systemic administration in humans

OBJECTIVE: To investigate the penetration of cefepime (a fourth generation cephalosporin) into the aqueous humor after single-dose intravenous administration in humans. PATIENTS AND METHODS: Before receiving cataract surgery, 30 patients received randomly 1 g (group 1, 15 patients) and 2 g (group 2, 15 patients) single intravenous injection of cefepime before surgery. Samples of aqueous humor and serum were obtained at 0.5, 1, 2, 4, and 12 hours after injection. Three patients were sampled each time for 1 g and 2 g of cefepime. Samples were assayed for cefepime concentrations with high performance liquid chromatography (HPLC). RESULTS: All the patients had detectable cefepime in their aqueous humor and serum measurable by HPLC. A mean peak aqueous humor level was 5.16 +/- 0.88 microg/mL in group 1 and 5.87 +/- 1.64 microg/mL in group 2 at 0.5 hour after injection. The mean level of cefepime in aqueous humor decreased after 0.5-hour measurements in both groups and was measured as 0.82 +/- 0.21 microg/mL in group 1 and 2.04 +/- 0.30 microg/mL in group 2 at 12 hours after injection. CONCLUSION: Aqueous humor levels of cefepime after single IV injection were above the minimum inhibitory concentration (MIC90) for most ocular pathogens, but the duration of exposure to an antibiotic was not sufficient for therapeutic effect.     

Comparative penetration of moxifloxacin and gatifloxacin in rabbit aqueous humor after topical dosing

PURPOSE: To evaluate the aqueous penetration of the fourth-generation fluoroquinolones moxifloxacin and gatifloxacin. SETTING: University of Arizona, Tucson, Arizona, USA. METHODS: Forty eyes of 20 New Zealand white rabbits were divided into 2 experimental groups. In Experiment I rabbits (20 eyes), a commercial preparation of topical gatifloxacin 0.3% was administered to 9 eyes and moxifloxacin 0.5% to 9 eyes; 2 eyes served as a control. Eyes were dosed according to a keratitis protocol; ie, every 15 minutes for 4 hours. The aqueous humor was sampled 10 minutes after the last dose. Experiment II rabbits (20 eyes) were dosed according to a cataract prophylaxis protocol; ie, 4 times a day for 10 days. The aqueous humor was sampled 1 hour after the last dose of antibiotic in 12 eyes and 24 hours after the last dose in 8 eyes. High-performance liquid chromatography was used to determine the fluoroquinolone concentration. RESULTS: In the keratitis dosing protocol, the mean concentration of moxifloxacin in the aqueous (n=9) was 11.057 microg/mL (range 7.66 to 18.87 microg/mL), which was significantly higher than the mean concentration of gatifloxacin (n=8) (7.570 microg/mL [range 4.75 to 10.86 microg/mL]) (P=.030). In the cataract prophylaxis dosing protocol, the mean aqueous concentration of moxifloxacin (n=6) was 1.745 microg/mL (range 0.92 to 3.87 mg/mL). The mean concentration of gatifloxacin (n=6) was 1.207 microg/mL (range 0.44 to 2.44 microg/mL). The difference was not statistically significant (P=.359). CONCLUSIONS: Higher mean levels (x1.46) of aqueous penetration were achieved with moxifloxacin than with gatifloxacin in the keratitis-dosing model. There was no statistically significant difference between the 2 drugs in the cataract prophylaxis dosing model. Both antibiotics had aqueous levels in excess of the minimum inhibitory concentration for most pathogenic organisms in both models.     

Diffusion of pefloxacin in the aqueous humor and crystalline lens after repeated oral administration in man

The intraocular penetration of pefloxacin was evaluated in 38 patients undergoing extracapsular cataract extraction. Patients were treated for three days with 400 mg of pefloxacin every twelve hours (the first dose being 800 mg). The mean maximum concentration of pefloxacin reached six hours after the last dose in the aqueous humor was 7.69 +/- 3.50 mg/l and reached twelve hours after the last dose in the lens was 4.59 +/- 3.15 micrograms/g. Antibiotic levels were measured by high performance liquid chromatography. Several doses until plasma steady state were effective in obtaining a higher level than a single dose of 400 mg. The ratio between aqueous humor and serum concentrations ranged between 0.50 and 0.89 (mean 68%). These concentrations in aqueous humor were higher than the MIC90 of pefloxacin for most bacterial pathogens involved in endophthalmitis 24 hours after the last dose.     

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.     

Aqueous humor levels of topically applied bupivacaine 0.75% in cataract surgery

PURPOSE: To measure the intraocular levels of bupivacaine 0.75% topically applied before phacoemulsification and to develop standards for topical anesthesia in cataract surgery. SETTING: Department of Ophthalmology, University Hospitals of Leicester, Leicester, United Kingdom. METHODS: Forty eyes having phacoemulsification for senile cataract under topical anesthesia without sedation were randomly assigned to 1 of 2 preoperative topical anesthesia regimens. Bupivacaine 0.75% was applied in 0.1 mL drops 3 times in the 30 minutes before surgery in 18 eyes and 6 times in the 60 minutes before surgery in 22 eyes. Aqueous humor and serum samples were taken at the start of surgery and the bupivacaine levels measured. A visual analog pain score scale was used to indicate intraoperative pain. RESULTS: The mean aqueous humor level of bupivacaine was 5.9 microg/mL +/- 4.3 (SD) after 3 drops and 5.7 +/- 4.0 microg /mL after 6 drops. The blood levels were less than 1.0 microg/mL. There was no statistically significant difference in the intraocular level of bupivacaine between the 2 groups. There was no difference in the age or sex distribution between the 2 groups, although there was an increase in the intraocular level of bupivacaine with age (approximately 1.4 microg/mL per decade; P =.048). There was no clear pattern associating the pain score with age, sex, or intraocular level of bupivacaine. CONCLUSIONS: A 3-drop regimen of bupivacaine 0.75% in the half hour before cataract surgery penetrated the eye as effectively as 6 drops in the 1 hour before surgery and provided good analgesia for phacoemulsification. Bupivacaine 0.75% penetrated the eye increasingly effectively with increasing age.