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C. Granvil, R. Siou-Mermet, T. Comstock, M. Jonasse, J. Proksch; Ocular Pharmacokinetics of Besifloxacin, a Novel Fluoroquinolone Antimicrobial Agent for Topical Ophthalmic Use, in Healthy Volunteers. Invest. Ophthalmol. Vis. Sci. 2008;49(13):873.
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To assess the ocular pharmacokinetics (PK) of besifloxacin, a novel fluoroquinolone in clinical development for bacterial conjunctivitis, following single topical ocular administration to healthy volunteers. The PK data were used along with in vitro antimicrobial MIC90 values for besifloxacin to assess the clinical PK/PD relationship for this anti-infective.
Sixty four healthy subjects were enrolled in this open-label study. Subjects received a single instillation of besifloxacin hydrochloride ophthalmic suspension (0.6% as free base) in the conjunctival sac of each eye. A single tear sample was collected on Schirmer tear strips from each subject at a predetermined time point with samples collected from separate groups over the 24 h after dosing. Besifloxacin concentrations in tear samples were analyzed by LC/MS/MS.
Following a single topical ocular dose, maximal besifloxacin concentrations in tears were observed within 10 min (Cmax of 610 ± 540 µg/g). Concentrations of 1.5 µg/g or higher were sustained for at least 24 h after dosing. Total exposure to besifloxacin in tears, based on AUC(0-24 h), was 1232 µg*h/g. Elimination of besifloxacin from tears occurred with an estimated half-life of 3.4 h. Both Cmax/MIC90 and AUC0-24h/MIC90 ratios were in excess of the minimum values associated with bacterial eradication against Staphylococcus aureus or Haemophilus influenzae. Results from PK modeling indicated that a TID dosing regimen would provide additional coverage and an improved PK/PD profile against other microorganisms.
Besifloxacin ophthalmic suspension afforded high besifloxacin concentrations in tears that were sustained for at least 24 h after a single dose. The combination of broad spectrum antimicrobial activity and PK/PD properties of besifloxacin support the continued clinical evaluation of besifloxacin for the treatment of bacterial conjunctivitis.
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