Concentrations of besifloxacin, gatifloxacin, and moxifloxacin in human conjunctiva after topical ocular administration

Abstract

Purpose: To evaluate the pharmacokinetic properties of besifloxacin, gatifloxacin, and moxifloxacin in the conjunctival tissue of healthy volunteers after topical application. Methods: One-hundred eight (108) subjects were randomly assigned to receive one drop of besifloxacin (0.6% suspension), gatifloxacin (0.3% solution), or moxifloxacin (0.5% solution) ophthalmic formulations in one eye prior to conjunctival biopsy. Conjunctival samples were taken from subjects at either 15 minutes, 30 minutes, 2 hours, 6 hours, 12 hours, or 24 hours after dosing. Results: All three fluoroquinolones reached a peak mean concentration 15 minutes after dosing. The mean concentrations of besifloxacin, gatifloxacin, and moxifloxacin at 15 minutes were 2.30 ± 1.42 µg/g, 4.03 ± 3.84 µg/g, and 10.7 ± 5.89 µg/g, respectively. Concentrations decreased with each subsequent time point. At 24 hours after dosing, concentrations of besifloxacin were measurable in 4 of 6 subjects, compared with 3 of 6 subjects for gatifloxacin and 2 of 6 subjects for moxifloxacin. Besifloxacin had the greatest mean residence time (4.7 hours) in the conjunctival tissue. With regard to methicillin-resistant strains of Staphylococcus aureus and Staphylococcus epidermidis, besifloxacin had the greatest area-under-the-curve (AUC) to MIC 90 ratio. Nine percent (9%) of study subjects (N = 7) experienced a transient reduction in visual acuity. Conclusion: All three fluoroquinolones were well tolerated and reached levels in the conjunctiva above the MIC 90 s of methicillin-sensitive S. aureus and S. epidermidis for at least 2 hours.

Integrated analysis of three bacterial conjunctivitis trials of besifloxacin ophthalmic suspension, 0.6%: etiology of bacterial conjunctivitis and antibacterial susceptibility profile

“…Topical administration of ocular antibiotics results in tear and conjunctival tissue concentrations often several-fold higher than the MIC, even if the latter is elevated due to development of resistance, raising the possibility that some antibacterials may be clinically effective even against bacterial strains with increased MICs. Nevertheless, the vitro potency of besifloxacin in conjunction with the favorable pharmacokinetic profile at the ocular surface 39 , 40 could provide a clinical advantage. After a single dose, besifloxacin exposure on the ocular surface results in C max /MIC and AUC 0–24 /MIC ratios that are well above the generally accepted pharmacodynamic ratios required for fluoroquinolone efficacy (ie, C max /MIC ≥ 10 and AUC 0–24 /MIC ≥ 30–50 for Gram-positive bacteria or ≥100–125 for Gram-negative bacteria) 41 – 43 even for drug-resistant staphylococcal isolates.…”

Integrated analysis of three bacterial conjunctivitis trials of besifloxacin ophthalmic suspension, 0.6%: microbiological eradication outcomes

“… 8 , 9 The average maximum tear concentration (C max ) of besifloxacin following instillation of a single drop of besifloxacin ophthalmic suspension, 0.6%, in healthy volunteers is 610 ± 540 μg/g, while the total exposure (AUC 0–24 [area under the curve from 0–24 hours]) is 1232 μg*h/g. 10 The average maximum conjunctival tissue concentration is 2.3 ± 1.42 μg/g. 11 The broad-spectrum antibacterial activity and pharmacokinetic properties of besifloxacin are consistent with observed effectiveness in bacterial conjunctivitis clinical trials.…”

Topical Antibiotic Therapy in the Ocular Environment: The Benefits of Using Moxifloxacin Eyedrops

“…Again, because of its pharmacological (pharmacodynamic and pharmacokinetic) features, moxifloxacin assures prolonged and effective concentrations on the conjunctiva with a few drops, avoiding the need for frequent doses. This implies that only a thrice-daily instillation for the whole therapy is effective, which is less than the usual topical quinolone regimen for the first days of therapy (up to eight instillations per day) [4,28]. Moreover, a reduced drug regimen may improve patient compliance, reducing the treatment failure rate [26].…”