June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
Solithromycin, a potent next-generation macrolide, for topical ophthalmic use
Author Affiliations & Notes
  • Kathryn S Crawford
    PharmOcu, Andover, Massachusetts, United States
  • Kevin L Ward
    Integral BioSystems, Bedford, Massachusetts, United States
  • Anne-Marie Cromwick
    Integral BioSystems, Bedford, Massachusetts, United States
  • Laura Kaminski
    Integral BioSystems, Bedford, Massachusetts, United States
  • Kara Keedy
    Cempra, Chapel Hill, North Carolina, United States
  • Prabhavathi Fernandes
    Cempra, Chapel Hill, North Carolina, United States
  • Shikha P Barman
    Integral BioSystems, Bedford, Massachusetts, United States
  • Footnotes
    Commercial Relationships   Kathryn Crawford, Cempra (C); Kevin Ward, Integral BioSystems (E); Anne-Marie Cromwick, Integral BioSystems (E); Laura Kaminski, Integral BioSystems (E); Kara Keedy, Cempra (E); Prabhavathi Fernandes, Cempra (E); Shikha Barman, Integral BioSystems (E)
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 1089. doi:
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      Kathryn S Crawford, Kevin L Ward, Anne-Marie Cromwick, Laura Kaminski, Kara Keedy, Prabhavathi Fernandes, Shikha P Barman; Solithromycin, a potent next-generation macrolide, for topical ophthalmic use. Invest. Ophthalmol. Vis. Sci. 2017;58(8):1089.

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

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Abstract

Purpose : Solithromycin (Soli) is a next-generation macrolide, the first fluoroketolide, which has activity against most macrolide-resistant strains. In addition to its antimicrobial properties, it has been shown to stimulate lysosome and lipid accumulation and overall differentiation of immortilized human meibomian gland epithelial cells, indicating its potential to treat meibomian gland disorder (MGD). However, since the molecule has low aqueous solubility, a suitable ophthalmic formulation was needed to assess the feasibility for topical ocular administration.

Methods : Formulation development evaluated the effects of various solubilizers and excipients on stability of solithromycin in solution. Soli concentration was analyzed by HPLC. Cornea permeability was assessed in a Franz-type diffusion ex-vivo bovine cornea permeability model. Tolerability and irritation potential was assessed in rabbits. Ocular pharmacokinetics in rabbits was calculated by LC/MS/MS bioanalyis of solithromycin concentrations in tears, cornea, aqueous humor, conjunctiva, and eyelids, 0.1-24 hours after administration of various modifications of the Soli ophthalmic formulation.

Results : A stable (6+ months at 5°C), Soli 1% ophthalmic solution was developed which met specifications for an ophthalmic solution and was well-tolerated and non-irritating in rabbits. Soli readily penetrates the cornea and ocular surface tissues, resulting in potentially effective intraocular concentrations (Cmax 80 ng/mL) as well as sustained levels in ocular surface tissues and tears for up to 12 hours after dosing (Cmax 20-1,800 µg/g).

Conclusions : Solithromycin can be formulated in a stable solution suitable for ophthalmic use. Soli is 8-16 times more potent than azithromycin in vitro and is active against azithromycin-resistant strains. Thus, Soli has the potential to treat a variety of ocular infections, as well as surface diseases such as MGD and blepharitis.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.

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