April 2014
Volume 55, Issue 13
ARVO Annual Meeting Abstract  |   April 2014
Pharmacodynamics and pharmacokinetics study of novel non-retinoid RBP4 antagonists
Author Affiliations & Notes
  • Boglarka Racz
    Department of Ophthalmology, Columbia University, New York, NY
  • Konstantin Petrukhin
    Department of Ophthalmology, Columbia University, New York, NY
  • Footnotes
    Commercial Relationships Boglarka Racz, None; Konstantin Petrukhin, Columbia University (P)
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science April 2014, Vol.55, 1955. doi:
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      Boglarka Racz, Konstantin Petrukhin; Pharmacodynamics and pharmacokinetics study of novel non-retinoid RBP4 antagonists. Invest. Ophthalmol. Vis. Sci. 2014;55(13):1955.

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

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Purpose: There is no FDA-approved treatment for the most prevalent dry (atrophic) form of AMD. RBP4 antagonists capable of inhibiting retinol-stimulated RBP4-TTR interaction demonstrate the ability to reduce bisretinoid accumulation in the retina and thus may be considered a potential therapy for dry AMD and Stargardt disease. Here we present the results of pharmacokinetics and pharmacodynamics characterization of novel non-retinoid RBP4 antagonists in rats.

Methods: Following a single oral or intravenous dose administration in male Sprague Dawley rats, plasma and urine samples were collected at different timepoints over the period of 48 hours. RBP4 levels were measured using the commercially available ELISA kit. Quantitative determination of compounds in rat biological fluids was accomplished by the use of protein precipitation and high-performance liquid chromatography with tandem mass spectrometric detection. Pharmacokinetic analysis was conducted using WinNonlin Version 4.1 package (Pharsight Corp.).

Results: We documented a significant 50-90% reduction of serum RBP4 in male Sprague Dawley rats in response to administration of RBP4 antagonists representing different structural series. Pharmacokinetics parameters for tested compounds were in line with the magnitude and duration of the RBP4 lowering.

Conclusions: RBP4 antagonists of different structural classes administered at pharmacological doses were well tolerated in our studies while inducing a significant reduction in plasma RBP4 levels. The preclinical pharmacokinetic profiles of test compounds appear to be satisfactory and consistent with their further development.

Keywords: 412 age-related macular degeneration • 503 drug toxicity/drug effects • 696 retinal degenerations: hereditary  

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