April 2014
Volume 55, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2014
Selective and sustained episcleral delivery of brimonidine: In vivo safety, toxiciy and pharmacokinetics
Author Affiliations & Notes
  • Ricardo De Carvalho
    3T Ophthalmics, Irvine, CA
  • Paulin Wahjudi
    3T Ophthalmics, Irvine, CA
  • Jonathan Moreno
    3T Ophthalmics, Irvine, CA
  • Claudia Mendes
    3T Ophthalmics, Irvine, CA
  • Pamela Ko
    3T Ophthalmics, Irvine, CA
  • Guilherme C Matsutani
    3T Ophthalmics, Irvine, CA
  • Footnotes
    Commercial Relationships Ricardo De Carvalho, 3T Ophthalmics (E), 3T Ophthalmics (I), 3T Ophthalmics (P); Paulin Wahjudi, 3T Ophthalmics (E); Jonathan Moreno, 3T Ophthalmics (E); Claudia Mendes, 3T Ophthalmics (E); Pamela Ko, 3T Ophthalmics (F); Guilherme Matsutani, 3T Ophthalmics (E)
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science April 2014, Vol.55, 449. doi:https://doi.org/
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      Ricardo De Carvalho, Paulin Wahjudi, Jonathan Moreno, Claudia Mendes, Pamela Ko, Guilherme C Matsutani; Selective and sustained episcleral delivery of brimonidine: In vivo safety, toxiciy and pharmacokinetics. Invest. Ophthalmol. Vis. Sci. 2014;55(13):449. doi: https://doi.org/.

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

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Abstract
 
Purpose
 

To characterize the safety, toxicity and pharamacokinetics of brimonidine delivered via a selective episcleral delivery system

 
Methods
 

In vitro elution studies were conducted in dissolution chambers. Ex vivo diffusion utilized rabbit sclera mounted in Franz chambers. New Zealand White rabbits were implanted with targeted-transscleral delivery systems (TTDS) containing a formulation of brimonidine in poly(lactic-co-glycolic) acid copolymer 85:15 lactic:glycolic acid ratios. Animals (n=3 per time point) were implanted at day 1 and sacrificed at 2, 3, 8, 15, 20 and 29 days of implantation for drug tissue analysis. Enucleated globes were frozen and bisected in two hemispheres—proximal and distal to the implant location. Choroid, retina and vitreous were dissected from the frozen enucleated globe were analyzed. Plasma samples were also collected and analyzed. Tissue analysis of brimonidine tartrate was carried out by HPLC-MS using a previously developed assay with a limit of detection (LOD) and limit of quantitation (LOQ) are 0.25 ng/mL and 0.50 ng/mL in the ocular samples.

 
Results
 

The distribution of brimonidine in the eye prioritized the proximal tissues forming a concentration gradient higher in the choroid followed by the retina and vitreous. The pharmacokinetics results are shown in the graph below. Therapeutic concentrations of brimonidines could be demonstrated throughout the follow period. At 29 days, only 30% of the drug content had been released. ERG and clinical examination up to 3 months disclosed no toxicity and tolerability concerns.

 
Conclusions
 

Sustained therapeutic concentrations of brimonidine were detected throughout the study period. Safety and tolerability was demonstrated. Selective episcleral delivery of brimonidine tartrate could provide long-term sustained delivery to the retina.

  
Keywords: 503 drug toxicity/drug effects • 615 neuroprotection • 697 retinal detachment  
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