Conjunctival tissue pharmacokinetic properties of topical azithromycin 1% and moxifloxacin 0.5% ophthalmic solutions: A single-dose, randomized, open-label, active-controlled trial in healthy adult volunteers

Background: Effective ocular tissue concentrations and prolonged residence times of antibacterial agents are important in treating both acute and chronic diseases. Conjunctival biopsy allows the determination of specific tissue concentration data for topical ophthalmic agents. Drug concentration analysis at various time points following instillation allows interpretation of the residence time and a rationale for dosing frequency. Objective: This study compared the pharmacokinetic parameters of 2 currently available topical ocular antibiotics-azithromycin ophthalmic solution 1% and moxifloxacin ophthalmic solution 0.5%-in the conjunctiva of healthy volunteers after a single topical administration. Methods: This single-dose, randomized, open-label, active-controlled clinical trial was conducted at ORA Clinical Research and Development, North Andover, Massachusetts. Subjects were randomly assigned to receive a single dose of azithromycin or moxifloxacin and to undergo biopsy sampling at 30 minutes or 2, 12, or 24 hours after administration. Concentrations of azithromycin and moxifloxacin were determined using liquid chromatography tandem mass spectrometry. Adverse events (AEs) were assessed at all visits using visual acuity measurements, slit-lamp biomicroscopy, and direct questioning. Results: Forty-eight subjects (mean age, 40.0 years; 48% female; 96% white, 2% black, and 2% Asian) underwent conjunctival biopsy. Mean (SD) concentrations of azithromycin in conjunctival tissue (lower limit of quantitation [LLOQ], 1 μg/g for 1-mg biopsy specimen) were 131 (89), 59 (19), 48 (24), and 32 (20) μg/g at 30 minutes and 2, 12, and 24 hours, respectively (median values, 117, 69, 46, and 30 μg/g). Mean concentrations concentrations of moxifloxacin in conjunctival tissue (LLOQ, 0.05 μg/g for 1-mg biopsy sample) were 1.92 (2.03), 3.77 (8.98), 0.02 (0.04), and 0.01 (0.02) μg/g at 30 minutes and 2, 12, and 24 hours, respectively (median values, 1.12, 0.12, <0.05, and <0.05 μg/g). Thirteen subjects (6 in the azithromycin group and 7 in the moxifloxacin group) experienced 20 AEs, 11 of which were considered possibly related to study treatment, and 15 of which were ocular (most commonly conjunctival hemorrhage). Conclusions: In this single-dose study of 2 currently available topical ocular antibiotics in healthy volunteers, therapeutic concentrations were achieved with both agents. Both treatments were well tolerated in the population studied. Clinical Trials Identification Number: NCT00564447.