Human Aqueous Humor Concentrations of Moxifloxacin Following Two Multiple–Dose Topical Ocular Dosing Regimens of Vigamox®.

Abstract

Abstract: : Purpose: To evaluate the ocular absorption of moxifloxacin HCI ophthalmic solution, 0.5% (Vigamox®) by measuring the concentration of moxifloxacin in the aqueous humor (AH) of patients undergoing cataract surgery following two different topical ocular dosing regimens. Methods: In an open–label, 2–arm, multiple–dose study, 60 cataract patients received moxifloxacin 0.5% according to one of two dosing regimens: operative eye treated with one drop every 15 min x 4 doses on day of surgery, or operative eye treated with one drop 4 times daily on the day prior to surgery, and one drop every 15 min x 4 doses on the day of surgery. Patients in both arms were randomized to one of 5 samplings times with the last dose 0.25, 0.50, 1, 2 or 3 hr prior to AH sampling. At the time of surgery approximately 0.15 mL of AH was collected from the anterior chamber using a tuberculin syringe and immediately placed in a storage container on dry ice. Samples were assayed using a validated LC–MS/MS method with a quantitation limit of 2.0 ng/mL. The mean concentration across at least 5 samples at each of 5 time points was calculated for each regimen. Results: Moxifloxacin was well absorbed and reached a mean (± SD) maximum concentration (C_max) of 1.84 ± 1.26 ug/mL at 1 hr post–dose for the 2–day regimen, and 1.50 ± 0.75 ug/mL at 30 min post–dose for the 1–day regimen. The C_max values for the two regimens were not significantly different (p>0.05). Absorption was rapid as indicated by mean aqueous concentrations >1 ug/mL at 15 min post–dose. One day post–operative slit–lamp evaluation was unremarkable relative to expected conjunctival and corneal wound healing, and no adverse events related to test article were reported during the study. Conclusions: Administration of Vigamox prior to cataract surgery had no effect on post–operative corneal and conjunctival healing. Moxifloxacin demonstrated rapid and extensive ocular absorption. The AH C_max was 25– to 30–fold above the median MICs for S aureus and S epidermidis isolates from clinical cases of endophthalmitis^a. There was no statistically significant difference in AH C_max between the 1– and 2–day regimens. ^a Mather R, et al. Fourth generation fluoroquinolones: new weapons in the arsenal of ophthalmic antibiotics. Am J Ophthal. 2002;133:463–466.

Keywords: antibiotics/antifungals/antiparasitics • anterior chamber