Moxifloxacin Hydrochloride Ophthalmic Solution Research Articles

Comparison of the Effects of Fourth-Generation Fluoroquinolones on Epithelial Healing After Photorefractive Keratectomy

To compare the effects of fluoroquinolones gatifloxacin and moxifloxacin used for antimicrobial prophylaxis after photorefractive keratectomy (PRK) on epithelial healing. Forty-four patients randomly received the prophylactic antibiotics gatifloxacin (Gatiflo; 0.3% gatifloxacin ophthalmic solution, Handok, Chungbuk, Korea, no preservative) in 1 eye and moxifloxacin (Vigamox; 0.5% moxifloxacin hydrochloride ophthalmic solution, Alcon Laboratories, Inc, Fort Worth, TX, no preservative) in the fellow eye after PRK. Corneal epithelium was circumferentially removed along a 7-mm zone mark. After PRK, all patients used topical antibiotics 4 times a day until the epithelium healed completely. Starting from postoperative day 1, epithelial healing times and defect sizes were recorded by slit-lamp examination and anterior segment photography. Postoperative pain and discomfort induced by the eyedrops were recorded. Additionally, therapeutic contact lenses were cultured to assess the antibacterial efficacy of fluoroquinolones. The mean epithelial healing times after PRK were similar for the 2 groups: 2.97 ± 0.41 days for gatifloxacin and 2.95 ± 0.48 days for moxifloxacin (P = 0.81). There was no statistically significant difference in mean defect size on each postoperative day between the treatment groups. There was no difference in postoperative pain and discomfort. No statistically significant differences were observed between eyes treated with gatifloxacin and moxifloxacin in terms of uncorrected visual acuity or best-corrected visual acuity at 3 months postoperatively. No significant differences were found in the effects of the preservative-free fourth-generation fluoroquinolones gatifloxacin and moxifloxacin on epithelial healing after PRK.

Ocular Pharmacokinetics/Pharmacodynamics of Besifloxacin, Moxifloxacin, and Gatifloxacin Following Topical Administration to Pigmented Rabbits

The purpose of this investigation was to evaluate the ocular pharmacokinetic/pharmacodynamic (PK/PD) relationship for besifloxacin, moxifloxacin, and gatifloxacin using rabbit ocular PK data, along with in vitro minimum inhibitory concentration (MIC90) values against methicillin- and ciprofloxacin-resistant Staphylococcus aureus (MRSA-CR) and Staphylococcus epidermidis (MRSE-CR). Rabbits received a topical instillation of Besivance™ (besifloxacin ophthalmic suspension, 0.6%), Vigamox (moxifloxacin hydrochloride ophthalmic solution, 0.5% as base), or Zymar (gatifloxacin ophthalmic solution, 0.3%), and ocular tissues and plasma were collected from 4 animals/treatment/collection time at 8 predetermined time intervals during the 24h after dosing. Ocular levels of each agent were measured by LC/MS/MS, and PK parameters (Cmax, Tmax, and AUC₀₋₂₄) were determined. AUC₀₋₂₄/MIC₉₀ ratios were calculated for tears, conjunctiva, cornea, and aqueous humor using previously reported MIC₉₀values for MRSA-CR and MRSE-CR. All of the fluoroquinolones tested demonstrated rapid penetration into ocular tissues after a single instillation. Besifloxacin demonstrated the highest exposure in tear fluid, while exposure in conjunctiva was comparable for all 3 compounds. Peak concentrations of all fluoroquinolones in aqueous humor were at or below ~1g/mL. In comparison with their MIC₉₀values against MRSE-CR and MRSA-CR, besifloxacin achieved an AUC₀₋₂₄/MIC₉₀ ratio of ~800 in tears, compared with values of ≤10 for moxifloxacin and gatifloxacin. In cornea, conjunctiva, and aqueous humor, the AUC₀₋₂₄/MIC₉₀ ratios were <10 for all compounds. However, in these tissues AUC₀₋₂₄/MIC₉₀ ratios for besifloxacin were 1.5- to 38-fold higher than moxifloxacin and gatifloxacin. In rabbits, besifloxacin demonstrates a nonclinical ocular PK profile characterized by high and sustained concentrations in tear fluid, resulting in AUC₀₋₂₄/MIC₉₀ ratios of ~800 for ciprofloxacin-resistant MRSE and MRSA after a single administration. Although besifloxacin had the highest AUC₀₋₂₄/MIC₉₀ratios for intraocular tissues, the ratios for all of the drugs were below the target values needed for effective bacterial killing of ciprofloxacin-resistant MRSE and MRSA. Taken together, these nonclinical data indicate that besifloxacin has a favorable ocular PK/PD profile, consistent with the reported clinical efficacy of besifloxacin in the treatment of bacterial conjunctivitis, and consistent with the profile needed for ocular surface sterilization.

Efficacy and Safety of Besifloxacin Ophthalmic Suspension 0.6% in Children and Adolescents with Bacterial Conjunctivitis

Acute conjunctivitis is the most frequent eye disorder seen by primary care physicians and one that often affects children. Besifloxacin is a new topical fluoroquinolone, the first chlorofluoroquinolone, for the treatment of bacterial conjunctivitis. To examine the efficacy and safety of besifloxacin ophthalmic suspension 0.6% in patients aged 1-17 years with bacterial conjunctivitis. This was a post hoc analysis of a subgroup of pediatric patients aged 1-17 years who had participated in three previously reported, randomized, double-masked, parallel-group, multicenter, clinical trials evaluating the safety and efficacy of besifloxacin in the treatment of bacterial conjunctivitis. The studies were conducted in a community setting (clinical centers). All three clinical trials included children (aged > or = 1 year) with a clinical diagnosis of bacterial conjunctivitis in at least one eye, based on the presence at baseline of grade 1 or greater purulent conjunctival discharge and conjunctival injection, and pin-hole visual acuity of at least 20/200 in both eyes for verbal patients. Two trials were vehicle controlled; the third trial was comparator controlled (moxifloxacin hydrochloride ophthalmic solution 0.5% as base). In all studies, besifloxacin ophthalmic suspension 0.6% was administered as one drop in the affected eye(s) three times daily, at approximately 6-hourly intervals, for 5 days. The main outcome measures were clinical resolution and microbial eradication at visit 2 (day 4 +/- 1 in one study; day 5 +/- 1 in the other two studies) and visit 3 (day 8 or 9). Data from the two vehicle-controlled studies were combined for the assessments to provide greater statistical power. This analysis included 815 pediatric patients aged 1-17 years (447 with culture-confirmed bacterial conjunctivitis). Clinical resolution was significantly greater (p < 0.05) in the besifloxacin group than in the vehicle group at both visit 2 (53.7% vs 41.3%) and visit 3 (88.1% vs 73.0%). Similarly, microbial eradication was significantly higher with besifloxacin than with vehicle at visit 2 (85.8% vs 56.3%) and visit 3 (82.8% vs 68.3%). No significant differences in clinical resolution and microbial eradication were noted between besifloxacin and moxifloxacin. Besifloxacin was well tolerated, with similar incidences of adverse events in the besifloxacin, vehicle, and moxifloxacin groups. Besifloxacin ophthalmic suspension 0.6% was shown to be safe and effective for the treatment of bacterial conjunctivitis in children and adolescents aged 1-17 years.

Comparison of 2 moxifloxacin regimens for preoperative prophylaxis: Prospective randomized triple-masked trial: Part 1: Aqueous concentration of moxifloxacin

To evaluate the aqueous concentration of moxifloxacin following 2 dosing regimens of topically administered moxifloxacin hydrochloride ophthalmic solution 0.5% (Vigamox). Iladevi Cataract & IOL Research Centre, Ahmedabad, India. In this prospective randomized triple-masked clinical trial, 156 patients having cataract surgery were randomly assigned to 1 of 2 regimens of preoperative prophylaxis. In Group A (n = 76), Vigamox was instilled 4 times a day 1 day before surgery plus 1 drop 2 hours before surgery (total of 5 drops). In Group B (n = 76), Vigamox was first instilled 2 hours before surgery and then every 15 minutes for 1 hour (total of 5 drops). In both groups, aqueous samples (0.1 mL) were collected within 2 hours of the first instillation on the day of surgery and stored at -80 degrees C. The antibiotic concentration in all aqueous aspirates was determined using high-performance liquid chromatography. Data were analyzed using the Kolmogorov-Smirnov t test; 95% confidence intervals (CIs) were calculated. The mean aqueous humor concentration of moxifloxacin was 1.58 microg/mL +/- 0.80 (SD) in Group A and 2.05 +/- 0.72 microg/mL in Group B (P<.0001; 95% CI, -0.72 to -0.22). Both dosing regimens produced substantially higher aqueous concentrations than the known minimum inhibitory concentration for Staphylococcus epidermidis. Topical moxifloxacin administered 2 hours before surgery achieved significantly higher aqueous concentrations than topical moxifloxacin administered 1 day before surgery with 1 drop given on the day of surgery.

Comparison of 2 moxifloxacin regimens for preoperative prophylaxis: Prospective randomized triple-masked trial: Part 2: Residual conjunctival flora

To determine whether a regimen of topical moxifloxacin hydrochloride ophthalmic solution 0.5% (Vigamox) administered on the day of cataract surgery reduces conjunctival bacterial flora. Iladevi Cataract & IOL Research Centre, Ahmedabad, India. Seventy-four patients were prospectively randomized to receive Vigamox 4 times 1 day before surgery plus 1 drop 2 hours preoperatively (Group 1) and 74 patients, to receive Vigamox 2 hours before surgery and every 15 minutes in the first hour only (Group 2). Conjunctival swabs from the upper and lower lid margins and lower fornix were taken before and after Vigamox instillation. Aliquots were spread on chocolate blood, anaerobic basal, and nutrient agars. The number of bacterial colony-forming units (CFU) on the plates was counted with a grid technique and expressed as log values. The total number of CFU per eye and mean percentage reduction in CFU after instillation were calculated. Bacterial species were identified using biochemical and biophysical reactions. Wilcoxon signed ranked and Mann-Whitney tests and multiple linear regression were applied. In Group 1, the median colony count decreased from 1284.00 CFU +/- 643.18 (SD) before Vigamox instillation to 65.00 +/- 72.61 CFU after instillation (93.12% reduction) (P<.001) and in Group 2, from 1634.00 +/- 769.27 CFU to 75.00 +/- 81.23 CFU (93.28% reduction) (P<.001). The percentage reduction after instillation was similar between the 2 groups (P = .09). Both Vigamox regimens reduced the number of CFU of conjunctival flora, indicating that instillation beginning on the day of surgery is effective.

Review of moxifloxacin hydrochloride ophthalmic solution in the treatment of bacterial eye infections

Moxifloxacin hydrochloride ophthalmic solution 0.5% (Vigamox((R))) is the ocular formulation/adaptation of moxifloxacin. Moxifloxacin is a broad spectrum 8-methoxyfluoroquinolone which terminates bacterial growth by binding to DNA gyrase (topoisomerase II) and topoisomerase IV, essential bacterial enzymes involved in the replication, translation, repair and recombination of deoxyribonucleic acid. Affinity for both enzymes improves potency and reduces the probability of selecting resistant bacterial subpopulations. Vigamox is a bactericidal, concentration dependent, anti-infective. It is preservative free, and well tolerated with minimal ocular side effects. It provides increased penetration into ocular tissues and fluids with improved activity against Streptococci and Staphylococci species and moderate to excellent activity against clinically relevant, gram-negative ocular pathogens.

Absorption of Topical Moxifloxacin Ophthalmic Solution Into Human Aqueous Humor

To investigate the absorption of moxifloxacin into human aqueous humor after administration of moxifloxacin hydrochloride ophthalmic solution, 0.5% as base. Cataract patients were randomly allocated to receive 1 drop every 15 minutes for 4 doses before surgery (group 1) or 1 drop 4 times per day on the day before surgery plus the same preoperative regimen as group 1 (group 2). The last dose was administered 0.25, 0.50, 1, 2, or 3 hours before aqueous humor sampling. Samples from 30 patients per group were analyzed by a validated HPLC/MS/MS method. For group 1, the mean +/- SD C(max) was 1.50 +/- 0.75 microg/mL and occurred at 0.5 hour after dosing. The mean C(max) for group 2 was 1.74 +/- 0.66 microg/mL and was reached at 1 to 2 hours. Mean AUC(0-3h) for groups 1 and 2 were 3.16 +/- 0.29 and 4.41 +/- 0.48 microg.h/mL, respectively. The difference in AUC(0-3h) was statistically significant (P = 0.04), but the difference in Cmax was not. Topical moxifloxacin was well absorbed. Maximum moxifloxacin concentrations were approximately 30 times higher than the median MICs for common pathogens in bacterial endophthalmitis, indicating that either regimen may provide sufficient concentrations to prevent postoperative endophthalmitis.