April 2014
Volume 55, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2014
Intracameral Conversion of Travoprost to Travoprost Acid in the Normotensive Beagle Dog Model
Author Affiliations & Notes
  • Leo Trevino
    Pharmaceutical Development, Envisia Therapeutics, Research Triangle Park, NC
  • Tomas Navratil
    Pharmaceutical Development, Envisia Therapeutics, Research Triangle Park, NC
  • RiLee Robeson
    Pharmaceutical Development, Envisia Therapeutics, Research Triangle Park, NC
  • Andres Garcia
    Pharmaceutical Development, Envisia Therapeutics, Research Triangle Park, NC
  • Janet Tully
    Pharmaceutical Development, Envisia Therapeutics, Research Triangle Park, NC
  • Michael Hunter
    Pharmaceutical Development, Envisia Therapeutics, Research Triangle Park, NC
  • Daria Stoltz
    Pharmaceutical Development, Envisia Therapeutics, Research Triangle Park, NC
  • Benjamin Maynor
    Pharmaceutical Development, Envisia Therapeutics, Research Triangle Park, NC
  • Brian C Gilger
    Ophthalmology, North Carolina State University, Raleigh, NC
  • Benjamin R Yerxa
    Pharmaceutical Development, Envisia Therapeutics, Research Triangle Park, NC
  • Footnotes
    Commercial Relationships Leo Trevino, Envisia Therapeutics (E); Tomas Navratil, Envisia Therapeutics (E); RiLee Robeson, Envisia Therapeutics (E); Andres Garcia, Envisia Therapeutics (E); Janet Tully, Envisia Therapeutics (E); Michael Hunter, Envisia Therapeutics (E); Daria Stoltz, Envisia Therapeutics (E); Benjamin Maynor, Envisia Therapeutics (E); Brian Gilger, Envisia Therapeutics (C); Benjamin Yerxa, Envisia Therapeutics (E)
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science April 2014, Vol.55, 5270. doi:
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      Leo Trevino, Tomas Navratil, RiLee Robeson, Andres Garcia, Janet Tully, Michael Hunter, Daria Stoltz, Benjamin Maynor, Brian C Gilger, Benjamin R Yerxa; Intracameral Conversion of Travoprost to Travoprost Acid in the Normotensive Beagle Dog Model. Invest. Ophthalmol. Vis. Sci. 2014;55(13):5270.

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

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Abstract
 
Purpose
 

When dosed as an eye drop for the treatment of glaucoma, topical prostaglandin analogs (PGAs), such as travoprost, undergo conversion to their biologically active acid forms as they cross the cornea into the aqueous humor, making them bioavailable at the putative target tissues in the trabecular meshwork and uveoscleral pathway. It has been reported that some PGAs do not readily convert to the acid form in human aqueous humor alone. (Guerra, F.L., et al, ARVO 2012) The goal of this work was to determine if travoprost, delivered from a biodegradable, intracameral implant is readily converted to its active form in normotensive Beagle dogs.

 
Methods
 

Biodegradable implant formulations containing travoprost (25 to 40 μg) were fabricated using a proprietary PRINT® technology and administered intracamerally in beagle dogs. Aqueous humor samples were collected at 14, 28, and 60 days postdose and tested for travoprost ester and travoprost acid. The acid was quantified directly by LC/MS/MS. To measure the ester, samples were incubated in rabbit liver esterase and tested for total travoprost acid. The ester concentration was calculated by the difference in travoprost acid concentration before and after treatment.

 
Results
 

The lower limit of quantitation (LLOQ) for travoprost acid was determined to be 10 pg/mL. The mole fraction of the travoprost acid, relative to the overall mass balance of ester and acid, in the aqueous humor was significantly higher than that of the ester for all three implant formulations at all of the time points (0.8 to 1.0 at all timepoints; see figure).

 
Conclusions
 

Our results indicate conversion of the travoprost ester to travoprost acid when travoprost ester is directly administered to the anterior chamber from biodegradable PRINT-based intracameral implants. Given these findings, extended release intracameral PGA implants may offer an attractive solution to the shortcomings of the current topical PGAs used for the treatment of elevated IOP.

 
 
Figure 1. Relative mole fractions of travoprost acid and travoprost in Beagle aqueous humor at 14, 28, and 60 days post dosing with biodegradable, PRINT intracameral implants
 
Figure 1. Relative mole fractions of travoprost acid and travoprost in Beagle aqueous humor at 14, 28, and 60 days post dosing with biodegradable, PRINT intracameral implants
 
Keywords: 568 intraocular pressure • 607 nanotechnology • 420 anterior chamber  
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