May 2007
Volume 48, Issue 13
ARVO Annual Meeting Abstract  |   May 2007
Nonclinical Ocular and Systemic Pharmacokinetics of BOL-303224-A, a Novel Fluoroquinolone Antimicrobial Agent for Topical Ophthalmic Use
Author Affiliations & Notes
  • J. Proksch
    Bausch & Lomb, Rochester, New York
    Drug Metabolism and Pharmacokinetics,
  • J.-Y. Driot
    Nonclinical Safety, Bausch & Lomb, Montpellier, France
  • K. W. Ward
    Bausch & Lomb, Rochester, New York
    Preclinical Development,
  • Footnotes
    Commercial Relationships J. Proksch, Bausch & Lomb, E; J. Driot, Bausch & Lomb, E; K.W. Ward, Bausch & Lomb, E.
  • Footnotes
    Support None.
Investigative Ophthalmology & Visual Science May 2007, Vol.48, 4273. doi:
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      J. Proksch, J.-Y. Driot, K. W. Ward; Nonclinical Ocular and Systemic Pharmacokinetics of BOL-303224-A, a Novel Fluoroquinolone Antimicrobial Agent for Topical Ophthalmic Use. Invest. Ophthalmol. Vis. Sci. 2007;48(13):4273.

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      © ARVO (1962-2015); The Authors (2016-present)

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Purpose:: Studies were conducted to evaluate the ocular pharmacokinetics (PK) of BOL-303224-A following single and repeated topical ocular administration to pigmented rabbits. These data were used along with in vitro antimicrobial MIC90 values for BOL-303224-A to assess the potential utility of this novel fluoroquinolone to treat ophthalmic infections.

Methods:: BOL-303224-A or [14C]BOL-303224-A was formulated as a 0.6% aqueous suspension containing polycarbophil, edetate disodium dihydrate, and sodium chloride. Animals received either a single instillation, or repeated (TID for 5 days) instillations. At predetermined intervals after the last dose, blood samples were collected from a marginal ear vein and tear samples were collected from each eye. Following collection of tear samples, animals were euthanized, eyes enucleated, and ocular tissues collected and frozen. Concentrations of BOL-303224-A in plasma and ocular tissues were quantified by LC/MS/MS; the level of carbon-14 in ocular and non-ocular tissues was analyzed by autoradiography or liquid scintillation analysis.

Results:: Following a single topical administration of a 0.6% formulation, BOL-303224-A readily penetrated into conjunctiva and aqueous humor, with maximum concentrations of 62791 ng/mL and 1692 ng/mL, respectively. The ocular mean residence time of BOL-303224-A was 7.1, 7.6, and 15.4 hr for tears, conjunctiva, and aqueous humor, respectively. PK modeling from these data indicated that BOL-303224-A is likely to demonstrate efficacy against most ophthalmologic pathogens with a TID dosing regimen. Systemic exposure to BOL-303224-A was low after topical ocular administration, with concentrations in plasma generally <10 ng/mL.

Conclusions:: The excellent ocular PK properties of BOL-303224-A along with the broad antimicrobial activity of this compound make it an excellent candidate for the treatment of a variety of ophthalmic infections.

Keywords: antibiotics/antifungals/antiparasitics • metabolism • anterior chamber 

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