title: Safety of moxifloxacin as shown in animal and in vitro studies.
abstract: Topical treatment of ocular bacterial infection is practiced widely, and the choice of the antibacterial agent depends on the nature of the infection, including the susceptibility of the organism, the tissue affected, and the safety profile of the agent. Moxifloxacin is a fourth-generation fluoroquinolone approved for ophthalmic use as moxifloxacin ophthalmic solution 0.5% (VIGAMOX, Alcon, Fort Worth, TX). Moxifloxacin ophthalmic solution 0.5% is self-preserved at a near-neutral pH of 6.8. In treating ocular infection, the three important aspects of therapeutic control are potency, penetration of the drug to the target site, and safety of the drug and the drug product. Moxifloxacin ophthalmic solution 0.5% provides antibacterial potency and high penetration of target ocular tissues. The ocular and systemic safety profile of moxifloxacin compares favorably with those of other fluoroquinolone antimicrobial agents, with a low risk of recognized quinolone-related toxicity. In vitro studies of fluoroquinolones with human or rabbit corneal epithelial cells or keratocytes suggest that moxifloxacin is similar in cytotoxicity potential to other drugs of this family. Specialized in vivo corneal wound-healing studies draw little distinction between moxifloxacin-treated eyes and those treated with other fluoroquinolones. Repeated-dose topical ocular studies in rabbits and monkeys, with high concentrations (up to 3%) of moxifloxacin and at treatment durations and regimens well in excess of label-prescribed use, demonstrated a high safety margin for ocular and extraocular tissues. Cornea, the tissue with highest exposure, was found to be unaffected by these high exposures, with slit-lamp biomicroscopy, corneal thickness measurement, intraocular pressure, and specular microscopy of the corneal endothelium (monkeys only), and histologic evaluation showing no effects, as compared with controls. Moxifloxacin ophthalmic solution 0.5% affords superior efficacy and ocular tissue penetration, with a favorable safety profile.
authors.affiliation: Alcon Research, Ltd., Fort Worth, Texas 76134-2099, USA.
authors.forename: David H
authors.initials: DH
authors.lastname: McGee
authors.forename: William F
authors.initials: WF
authors.lastname: Holt
authors.forename: Philip R
authors.initials: PR
authors.lastname: Kastner
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Rice
mesh_terms: D000818:Animals; D001372:Aza Compounds / Q000008:administration & dosage / Q000633:toxicity*; D001419:Bacteria / Q000187:drug effects; D003320:Corneal Ulcer / Q000188:drug therapy / Q000382:microbiology; D019573:Epithelium, Corneal / Q000187:drug effects; D015818:Eye Infections, Bacterial / Q000188:drug therapy / Q000382:microbiology; D024841:Fluoroquinolones; D000077266:Moxifloxacin; D009883:Ophthalmic Solutions / Q000008:administration & dosage / Q000633:toxicity; D011804:Quinolines / Q000008:administration & dosage / Q000633:toxicity*; D014945:Wound Healing / Q000187:drug effects
chemical_list: D001372:Aza Compounds; D024841:Fluoroquinolones; D009883:Ophthalmic Solutions; D011804:Quinolines; D000077266:Moxifloxacin