Ocular Pharmacokinetics of Besifloxacin Following Topical Administration to Rabbits, Monkeys, and Humans

Proksch, Joel W.; Granvil, Camille; Siou-Mermet, Raphaële; Comstock, Timothy L.; Paterno, Michael R.; Ward, Keith W.

doi:10.1089/jop.2008.0116

Cited by 61 publications

(55 citation statements)

References 29 publications

(43 reference statements)

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“…A previous PK study for besifloxacin revealed that the maximum besifloxacin concentrations in tear fluid after a single instillation were 610 µg/g, which is approximately 265-fold higher than the maximum besifloxacin concentration observed in conjunctiva in the present study. 23 At 24 hours after a single dose, besifloxacin concentrations in tears were approximately 50-fold higher than the conjunctival concentrations detected in this study. The concentration of drug in the tear may act synergistically with conjunctival drug concentration to contribute to the effective treatment of bacterial conjunctivitis.…”

Section: Discussioncontrasting

confidence: 58%

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

Torkildsen

Proksch²,

Shapiro³

et al. 2010

OPTH

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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.

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Section: Discussioncontrasting

confidence: 58%

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

Torkildsen

Proksch²,

Shapiro³

et al. 2010

OPTH

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“…Proksch et al 18 found that the concentration of besifloxacin was comparable to that of moxifloxacin in the anterior chamber of rabbits and monkeys. Our study indicates that these data may not be analogous to the clinical situation in human eyes.…”

Section: Discussionmentioning

confidence: 98%

Aqueous penetration of moxifloxacin 0.5% ophthalmic solution and besifloxacin 0.6% ophthalmic suspension in cataract surgery patients

Yoshida

Kim

Pratzer

et al. 2010

Journal of Cataract and Refractive Surgery

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“…The consistently improved activity profile of besifloxacin against gram-positive and gram-negative pathogens that were resistant to other fluoroquinolones was particularly notable. In conjunction with recently reported safety, efficacy, and pharmacokinetic results from clinical trials (14,16,18,21), besifloxacin's broad-spectrum activity profile is appropriate for empirical treatment of bacterial infections. …”

mentioning

confidence: 99%

Besifloxacin, a Novel Fluoroquinolone, Has Broad-Spectrum In Vitro Activity against Aerobic and Anaerobic Bacteria

Haas¹,

Pillar

Zurenko³

et al. 2009

Antimicrob Agents Chemother

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The antibacterial spectrum of besifloxacin, a novel fluoroquinolone recently approved for treatment of ocular infections, was studied using 2,690 clinical isolates representing 40 species. Overall, besifloxacin was the most potent agent tested against gram-positive pathogens and anaerobes and was generally equivalent to comparator fluoroquinolones in activity against most gram-negative pathogens. Besifloxacin demonstrated potent, broad-spectrum activity, which was particularly notable against gram-positive and gram-negative isolates that were resistant to other fluoroquinolones and classes of antibacterial agents.Bacterial conjunctivitis is an inflammation of the transparent mucous membrane covering the globe of the eye. This common ocular surface infection is caused by a broad variety of bacteria and is usually treated with broad-spectrum topical ophthalmic antibacterials (1,13,19,20). The increasing prevalence of drug-resistant ocular isolates highlights the need for the development of new agents for the treatment of bacterial infections (8). Besifloxacin ( Fig. 1) is a novel 8-chloro-fluoroquinolone agent with potent, bactericidal activity against prevalent and drug-resistant pathogens (6). Clinical development of the agent for use as a topical ophthalmic agent has been completed, and the agent has demonstrated consistent safety and efficacy in three bacterial conjunctivitis clinical trials (14,16,21). Pharmacokinetic studies demonstrated that after a single topical dose of 0.6% besifloxacin ophthalmic suspension, mean besifloxacin levels in human tears ranged from 610 g/ml at 10 min postadministration to 1.6 g/ml at 24 h postadministration (12). Here, the in vitro activity of besifloxacin against a broad range of aerobic and anaerobic bacterial species, including problematic drug-resistant strains, was evaluated.Totals of 2,535 aerobic and 155 anaerobic bacterial clinical isolates from Eurofins Medinet (Chantilly, VA) were selected for the study. The majority of isolates were from 2005 to 2008, and wherever possible, isolates were from ocular and respiratory specimens of U.S. origin. Susceptibility testing was conducted per Clinical and Laboratory Standards Institute reference methods (9-11).Activity of besifloxacin against gram-positive aerobes. Against Enterococcus faecalis and E. faecium, including vancomycin-resistant enterococci, besifloxacin was more potent than the comparator fluoroquinolones, as well as azithromycin, vancomycin, and tobramycin (Table 1). Besifloxacin further demonstrated excellent activity against Listeria monocytogenes, similar to that of tobramycin and penicillin and better than that observed with comparator fluoroquinolones.For Staphylococcus aureus and S. epidermidis, previously reported MIC 50 s/MIC 90 s were consistent with current besifloxacin values for quinolone-susceptible and quinolone-resistant subsets (3,5,14). Besifloxacin was especially potent against ciprofloxacin-resistant isolates; for example, the MIC 90 s for non-ciprofloxacin-susceptible S. aureus were 4 g/ml for...

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Ocular Pharmacokinetics of Besifloxacin Following Topical Administration to Rabbits, Monkeys, and Humans

Abstract: Taken together, the results of the current investigation provide a PK/PD-based rationale that supports the use of besifloxacin for the safe and effective treatment of ocular infections.

Cited by 61 publications

References 29 publications

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

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

Aqueous penetration of moxifloxacin 0.5% ophthalmic solution and besifloxacin 0.6% ophthalmic suspension in cataract surgery patients

Besifloxacin, a Novel Fluoroquinolone, Has Broad-Spectrum In Vitro Activity against Aerobic and Anaerobic Bacteria

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